EP1968684A2 - Nasenverstopfung, obstruktionslinderung und arzneiabgabe - Google Patents

Nasenverstopfung, obstruktionslinderung und arzneiabgabe

Info

Publication number
EP1968684A2
EP1968684A2 EP06840036A EP06840036A EP1968684A2 EP 1968684 A2 EP1968684 A2 EP 1968684A2 EP 06840036 A EP06840036 A EP 06840036A EP 06840036 A EP06840036 A EP 06840036A EP 1968684 A2 EP1968684 A2 EP 1968684A2
Authority
EP
European Patent Office
Prior art keywords
nasal
nasal insert
polymer
insert
orifice
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP06840036A
Other languages
English (en)
French (fr)
Other versions
EP1968684A4 (de
EP1968684B1 (de
Inventor
Ernest Santin
Louise S. Macdonald
Scott D. Macdonald
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanostec Corp
Original Assignee
Sanostec Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sanostec Corp filed Critical Sanostec Corp
Publication of EP1968684A2 publication Critical patent/EP1968684A2/de
Publication of EP1968684A4 publication Critical patent/EP1968684A4/de
Application granted granted Critical
Publication of EP1968684B1 publication Critical patent/EP1968684B1/de
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F5/00—Orthopaedic methods or devices for non-surgical treatment of bones or joints; Nursing devices; Anti-rape devices
    • A61F5/01—Orthopaedic devices, e.g. splints, casts or braces
    • A61F5/08—Devices for correcting deformities of the nose ; Devices for enlarging the nostril, e.g. for breathing improvement
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F5/00—Orthopaedic methods or devices for non-surgical treatment of bones or joints; Nursing devices; Anti-rape devices
    • A61F5/56—Devices for preventing snoring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/08—Inhaling devices inserted into the nose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/08—Inhaling devices inserted into the nose
    • A61M15/085—Fixing means therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/06—Respiratory or anaesthetic masks
    • A61M16/0666—Nasal cannulas or tubing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/10—Preparation of respiratory gases or vapours
    • A61M16/105—Filters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/10—Preparation of respiratory gases or vapours
    • A61M16/105—Filters
    • A61M16/106—Filters in a path
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M29/00—Dilators with or without means for introducing media, e.g. remedies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A—HUMAN NECESSITIES
    • A62—LIFE-SAVING; FIRE-FIGHTING
    • A62B—DEVICES, APPARATUS OR METHODS FOR LIFE-SAVING
    • A62B23/00—Filters for breathing-protection purposes
    • A62B23/06—Nose filters

Definitions

  • This disclosure pertains to methods and devices for nasal congestion, obstruction relief, and nasal drug delivery, and in particular to methods and devices for improving nasal breathing, treatment of sinus conditions, and reducing snoring.
  • Snoring is a condition characterized by rough, loud, rattling breathing, or aspiratory noise in the throat during- sleep or deep coma.
  • the characteristic snoring noise is produced by vibration of the son palate (the son tissue in lhe roof of the mouth near the throat) or vocal chords by inhaled or exhaled air. As the soft palate vibrates, the lips, cheeks, and nostrils may also vibrate, making the snoring louder.
  • Snoring can be caused by underlying physical or disease conditions that restrict air passages and force the patient to breathe through their mouth with exaggerated force to move air through narrowed nasal passages.
  • Chronic snoring can be the result of obstruction of nasal airways, septal deviation, or obstructed nasal passages.
  • Temporary snoring, or a sudden onset of snoring can be the result of congestion or swollen nasal mucus membranes, as with a cold or hay fever, or a nasal polyp.
  • Snoring can cause relationship problems between partners, and lead to a loss of intimacy and deterioration of relationships. Loss of sleep, or insufficient rest during sleep increases irritability, reduces memory and concentration, and decreases work performance.
  • a number of methods and devices have been developed to reduce or eliminate snoring. Some devices are external to the patient and include buzzer systems and alarms that wake the patient. Special pillows, neck collars, chin braces and head straps have also been tested in an effort to control snoring.
  • anatomical obstructions such as removing tonsils, or correcting medium hypertrophy, or septal deviation.
  • UPPP Uvulopalatopharyngoplasty
  • Tin ' s procedure acts like an internal facelift, tightening loose tissue.
  • Other remedies for chronic sinusitis or snoring include prescription antibiotics, herbal and homeopathic rinses, sprays or potions, and OTC medications such as decongestants and anti-histamines. Diet and lifestyle changes may reduce snoring to some degree. Nasal valve collapse is a soft tissue condition that is inoperable. Remedies are limited to rigid and metal spring like products. Use of these type of products is limited due to the discomfort or metal taste.
  • Sinusitis is another common nasal disease. Sinusitis is inllam ⁇ ialion or infection of the mucous membranes that line the inside of the nose and sinuses. It can be caused by bacteria, viruses, and possibly by allergies. Chronic sinusitis is a prolonged sinus infection which generally last longer than 12 weeks. Chronic sinusitis is difficult to treat because it responds slowly to medications. Conventional treatment for chronic sinusitis includes oral antibiotics, nasal spray, and sinus surgery. These treatments generally cannot get directly to the source of the problem, or they may cause undesirable side effects.
  • the disclosed devices and methods may be used to increase airflow through the nasal passages. Such increase can help reduce or eliminate a wide variety of nasal, sinus, and upper airway disorders, including snoring, sleep apnea, nasal congestion, and nasal obstruction.
  • the disclosed devices and methods may also be used to treat chronic sinusitis, rhinitis, and allergies.
  • a nasal insert may include a wall in the shape of a tube, the wall including a first end defining a first orifice and a second end defining a second orifice.
  • the first end may have a diameter, diagonal , measurement, or cross-sectional area larger than that of the second end.
  • the first end may include at least one thinned or webbed portion that is more flexible that the rest of the first end.
  • the second end may completely encircle the second orifice.
  • the coupler element maintains the tubular elements in a generally parallel relationship to each other in a common plane and in a spaced-apart relation which corresponds generally to the separation between the user's nostrils.
  • the coupler element is a resilient, nominally curved strut lying in a plane substantially perpendicular to the tube axes, permitting relative angular motion of the tube elements about an axis perpendicular to the tube axes.
  • a "single tube" nasal breathing assist device is a single, opcn-cndcd, resilient tubular element, adapted for insertion into a user's nostril.
  • the tubular element is conic-frustum shaped, having a relatively large diameter first end and a relatively smaller diameter second end, and a taper extending from the first end to the second end along a tube axis.
  • the tubular element may have passageways extending through the tubular element transverse to the tube axis. In one form, these passageways may be elongated.
  • the single tube may be used in a user's nostril, and if desired, together with another single tube in the user's other nostril. In this form, the tubes are not coupled to each other.
  • the tubular elements have a tab extending from the first (i.e. relatively large) end which extends substantially parallel to the tube axis and is elongated in the direction of the tube axis.
  • each tube element has a tab support extending radially from the first end in a direction substantially perpendicular to the tube axis. At least one tab extends from the tab support, and is elongated in the direction of the tube axis.
  • the tabs may be resiliently deformable, so as to permit elastic deformation in use, providing a frictional holding force when engaging the nose.
  • the tabs may be non-resiliently deformable, permitting inelastic deformation, so that a user can "pinch” the tabs so that they capture and hold the nose.
  • the non-resilient tabs are preferably made with a stiffening material embedded in, affixed to, or of plastic or metal, for example, copper, aluminum, but may be made of other materials that may be non-resiliently deformed.
  • the tab preferably includes at least one relatively small protrusion extending from a distal end of the tab. The distal end is distal from the first end of the tubular element. The relatively small protrusion may also extend from the outer surface of the tubular elemenl opposing the distal end of the lab. The tab and the protrusion help to prevent the device from slipping out of a user's nose.
  • the protrusion extends throughout an inner circumference of the channel.
  • the filter includes a liner portion extending along a central axis between a relatively large end and a relatively small end, and a filter medium spanning at least one of the relatively large end and the relatively small end.
  • the liner portion and the filter medium arc integrally constructed from a sheet or composite of a filter medium.
  • FIG. 1 is a perspective view of one embodiment of the present invention
  • FlG. 3B shows a side view of the embodiment of FiG. 3 A rotated about an axis
  • FIG.4A is a perspective view of an alternate embodiment of (lie invention
  • FlG.4B is a perspective view of another alternate embodiment of the invention.
  • FIGS. 5A-E are perspective views of alternate embodiments of the invention.
  • FIG. 7 shows a cross-sectional view of an alternate embodiment of the invention
  • FIG. 8 shows the filter of FIG. 6 together with the nasal breathing assist device
  • FIG. 9 shows another preferred embodiment of the invention.
  • FIG. 1OA shows a schematic view of a filter in accordance with one preferred embodiment of the present invention.
  • FIG. 1OB shows a schematic view of a filter in accordance with another preferred embodiment of the present invention.
  • FIG. 1 IA shows a perspective view of another preferred embodiment of the present invention
  • FIG. 1 IB shows a perspective view of another preferred embodiment of the present invention.
  • FIG. 12 is a representation of one embodiment of the invention in use.
  • FIGS. 13-21 depict additional devices embodying various disclosed features.
  • FIGS. 1 through 10 The nasal breathing assist devices according to the various aspects of the invention are shown in FIGS. 1 through 10. These devices overcome the deficiencies in the currently available devices.
  • the illustrated devices are small, inconspicuous in use, and require no special attachments or fittings, although they may be combined with other devices, such as cannulas.
  • the devices arc worn inside the nose, so that the nasal passages arc kept open from the inside, rather than by external means. This allows the devices to maintain airways in noses where nasal obstructions, inflammatory or structural anatomical deviations diminish the effectiveness of externally applied strips.
  • the devices can be used alone, or in conjunction with decongestant and antihistamines powders, tablets or liquid medications, other snore-reducing aids, such as pillows, or medicated nasal sprays.
  • the term "access device” is an art-recognized term and includes any medical device adapted for gaining or maintaining access to an anatomic area. Such devices are familiar to artisans in the medical and surgical fields.
  • An access device may be a needle, a catheter, a cannula, a trocar, a tubing, a shunt, a drain, or an endoscope such as an otoscope, nasopharyngoscope, bronchoscope, or any other medical device suitable for entering or remaining positioned within the preselected anatomic area.
  • biocompatible polymer and “biocompatibility” when used in relation to polymers are art-recognized.
  • biocompatible polymers include polymers that are generally neither themselves toxic to the host, nor degrade (if the polymer degrades) at a rate that produces monomcric or oligomcric subunits or other byproducts at toxic concentrations in the host.
  • biodegradation generally involves degradation of the polymer in a host, e.g., into its monomeric subunits, which may be known to be effectively non-toxic. Intermediate oligomeric products resulting from such degradation may have different lexicological properties, however, or biodegradation may involve oxidation or other biochemical reactions that generate molecules other than monomeric subunits of the polymer.
  • Such assays are well known in the art.
  • One example of such an assay may be performed with live carcinoma cells, such as GT3TKB tumor cells, in the following manner: the sample is degraded in 1 M NaOH at 37 0 C until complete degradation is observed. The solution is then neutralized with IM HCl. About 200 ⁇ L of various concentrations of the degraded sample products are placed in 96-well tissue culture plates and seeded with human gastric carcinoma cells (GT3TKB) at 10 4 /well density. The degraded sample products are incubated with the GT3TKB cells for 48 hours.
  • GT3TKB human gastric carcinoma cells
  • results of the assay may be plotted as % relative growth vs. concentration of degraded sample in the tissue-culture well.
  • polymers and formulations may also be evaluated by well-known in vivo tests, such as subcutaneous implantations in rats to confirm that they do not cause significant levels of irritation or inflammation at the subcutaneous implantation sites.
  • biodegradable is art-recognized, and includes polymers, compositions and formulations, such as those described herein, that are intended to degrade during use.
  • Biodegradable polymers typically differ from non-biodegradable polymers in that the former may be degraded during use.
  • such use involves in vivo use, such as in vivo therapy, and in other certain embodiments, such use involves in vitro use.
  • degradation attributable to biodegradability involves the degradation of a biodegradable polymer into its component subunits, or digestion, e.g., by a biochemical process, of the polymer into smaller, non-polymeric subunits.
  • biodegradation may generally be identified.
  • one type of biodegradation may involve cleavage of bonds (whether covalent or otherwise) in the polymer backbone.
  • monomers and oligomers typically result, and even more typically, such biodegradation occurs by cleavage of a bond connecting one or more of subunits of a polymer.
  • another type of biodegradation may involve cleavage of a bond (whether covalent or otherwise) internal to side chain or that connects a side chain to the polymer backbone.
  • a therapeutic agent or other chemical moiety attached as a side chain to the polymer backbone may be released by biodegradation.
  • one or the other or both generally types of biodegradation may occur during use of a polymer.
  • biodegradation encompasses both general types of biodegradation.
  • the degradation rate of a biodegradable polymer often depends in part on a variety of factors, including the chemical identity of the linkage responsible for any degradation, the molecular weight, crystallinity, biostability, and degree of cross-linking of such polymer, the physical characteristics of the implant, shape and size, and the mode and location of administration. For example, the greater the molecular weight, the higher the degree of crystallinity, and/or the greater the biostability, the biodegradation of any biodegradable polymer is usually slower.
  • biodegradable is intended to cover materials and processes also termed "bioerodible".
  • the biodegradation rate of such polymer may be characterized by a release rate of such materials. In such circumstances, the biodegradation rate may depend on not only the chemical identity and physical characteristics of the polymer, but also on the identity of any such material incorporated therein.
  • polymeric formulations biodegrade within a period that is acceptable in the desired application.
  • such degradation occurs in a period usually less than about five years, one year, six months, three months, one month, fifteen days, five days, three days, or even one day on exposure to a physiological solution with a pH between 6 and 8 having a temperature of between 25 and 37 °C.
  • the polymer degrades in a period of between about one hour and several weeks, depending on the desired application.
  • drug delivery device is an art-rccognizcd term and refers to any medical device suitable for the application of a drug to a targeted organ or anatomic region.
  • the term includes those devices that transport or accomplish the instillation of the compositions towards the targeted organ or anatomic area, even if the device itself is not formulated to include the composition.
  • a needle or a catheter through which lhe composition is inserted into an anatomic area or into a blood vessel or other structure related to the anatomic area is understood to be a drug delivery device.
  • a stent or a shunt or a catheter that has the composition included in its substance or coated on its surface is understood to be a drug delivery device.
  • sustained release When used with respect to a therapeutic agent or other material, the term "sustained release" is art-recognized.
  • a subject composition that releases a substance over time may exhibit sustained release characteristics, in contrast to a bolus type administration in which the entire amount of the substance is made biologically available at one time.
  • the polymer matrices upon contact with body fluids including blood, tissue fluid, lymph or the like, may undergo gradual degradation (e.g., through hydrolysis) with concomitant release of any material incorporated therein, for a sustained or extended period (as compared to the release from a bolus). This release may result in prolonged delivery of therapeutically effective amounts of any incorporated a therapeutic agent.
  • Sustained release will vary in certain embodiments as described in greater detail below.
  • parenteral administration and “administered parenterally” are art-recognized terms, and include modes of administration other than enteral and topical administration, such as injections, and include, without limitation, intravenous, intramuscular, intrapleural, intravascular, intrapericardial, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intranasal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intra-articular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.
  • treating includes preventing a disease, disorder or condition from occurring in an animal which may be predisposed to the disease, disorder and/or condition but has not yet been diagnosed as having it; inhibiting the disease, disorder or condition, e.g., impeding its progress; and relieving the disease, disorder or condition, e.g., causing regression of the disease, disorder and/or condition. Treating the disease or condition includes ameliorating at least one symptom of the particular disease or condition, even if the underlying pathophysiology is not affected.
  • fluid is art-recognized to refer to a non-solid state of matter in which the atoms or molecules are free to move in relation to each other, as in a gas or liquid. If unconstrained upon application, a fluid material may flow to assume the shape of the space available to it, covering for example, the surfaces of an excisional site or the dead space left under a flap. A fluid material may be inserted or injected into a limited portion of a space and then may flow to enter a larger portion of the space or its entirety.
  • Such a material may be termed "flowablc.”
  • This term is art-rccognizcd and includes, for example, liquid compositions that are capable of being sprayed into a site; injected with a manually operated syringe fitted with, for example, a 23-gauge needle; or delivered through a catheter.
  • flowable include those highly viscous, "gel-like" materials at room temperature that may be delivered to the desired site by pouring, squeezing from a tube, or being injected with any one of the commercially available injection devices that provide injection pressures sufficient to propel highly viscous materials through a delivery system such as a needle or a catheter.
  • a composition comprising it need not include a biocompatible solvent to allow its dispersion within a body cavity. Rather, the flowable polymer may be delivered into the body cavity using a delivery system that relies upon the native flowability of the material for its application to the desired tissue surfaces. For example, if flowable, a composition comprising polymers can be injected to form, after injection, a temporary biomechanical barrier to coat or encapsulate internal organs or tissues, or it can be used to produce coatings for solid implantable devices. In certain instances, flowable subject compositions have the ability to assume, over time, the shape of the space containing it at body temperature.
  • Viscosity is understood herein as it is recognized in the art to be the internal friction of a fluid or the resistance to flow exhibited by a fluid material when subjected to deformation.
  • the degree of viscosity of the polymer may be adjusted by the molecular weight of the polymer and other methods for altering the physical characteristics of a specific polymer will be evident to practitioners of ordinary skill with no more than routine experimentation.
  • the molecular weight of the polymer used may vary widely, depending on whether a rigid solid state (higher molecular weights) desirable, or whether a fluid state (lower molecular weights) is desired.
  • compositions, polymers and other materials and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.
  • materials which may serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such, as peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) al
  • pharmaceutically acceptable salts is art-recognized, and includes relatively non-toxic, inorganic and organic acid addition salts of compositions, including without limitation, therapeutic agents, excipients, other materials and the like.
  • pharmaceutically acceptable salts include those derived from mineral acids, such as hydrochloric acid and sulfuric acid, and those derived from organic acids, such as ethanesulfonic acid, benzenesulfonic acid, p-Loluenesulfonic acid, and the like.
  • suitable inorganic bases for die formation of sails include the hydroxides, carbonates, and bicarbonates of ammonia, sodium, lithium, potassium, calcium, magnesium, aluminum, zinc and the like.
  • Salts may also be formed with suitable organic bases, including those that are non-toxic and strong enough to form such salts.
  • the class of such organic bases may include mono-, di-, and trialkylamines, such as methylamine, dimethylamine, and triethylaniine; mono-, di- or trihydroxyalkylamines such as mono-, di-, and trietlianolamine; amino acids, such as arginine and lysine; guanidine; N-methylglucosamine; N-methylglucamine; L-glutamine; N-methylpiperazine; morpholine; ethylenediamine; N-benzylphenethylamine; (trihydroxymethyl)aminoethane; and the nice.
  • a "patient,” “subject,” or “host” to be treated by the subject method may mean either a human or non-human animal, such as primates, mammals, and vertebrates.
  • prophylactic or therapeutic treatment is art-recognized and includes administration to the host of one or more of the subject compositions. If it is administered prior to clinical manifestation of the unwanted condition (e.g., disease or other unwanted state of the host animal) then the treatment is prophylactic, i.e., it protects the host against developing the unwanted condition, whereas if it is administered after manifestation of the unwanted condition, the treatment is therapeutic (i.e., it is intended to diminish, ameliorate, or stabilize the existing unwanted condition or side effects thereof).
  • the unwanted condition e.g., disease or other unwanted state of the host animal
  • therapeutic agent include molecules and other agents that are biologically, physiologically, or pharmacologically active substances that act locally or systemically in a patient or subject to treat a disease or condition.
  • the terms include without limitation, medicaments; vitamins; mineral supplements; substances used for the treatment, prevention, diagnosis, cure or mitigation of disease or illness; or substances which affect the structure or function of the body; or pro-drugs, which become biologically active or more active after they have been placed in a predetermined physiological environment.
  • Such agents may be acidic, basic, or salts; they may be neutral molecules, polar molecules, or molecular complexes capable of hydrogen bonding; they may be prodrugs in the form of ethers, esters, amides and the like that are biologically activated when administered into a patient or subject.
  • the phrase 'therapeutically effective amount is an art-recognized term.
  • the term refers to an amount of a therapeutic agent that, when incorporated into a polymer, produces some desired effect at a reasonable benefit/risk ratio applicable to any medical treatment.
  • the term refers to that amount necessary or sufficient to eliminate, reduce or maintain (e.g., prevent the spread of) a tumor or other target of a particular therapeutic regimen.
  • the effective amount may vary depending on such factors as the disease or condition being treated, the particular targeted constructs being administered, the size of the subject or the severity of the disease or condition. One of ordinary skill in the art may empirically determine the effective amount of a particular compound without necessitating undue experimentation.
  • preventing when used in relation to a condition, such as a local recurrence, a disease such as cancer, a syndrome complex such as heart failure or any other medical condition, is well understood in the art, and includes administration of a composition which reduces the frequency of, or delays the onset of, symptoms of a medical condition in a subject relative to a subject which does not receive the composition.
  • prevention of cancer includes, for example, reducing the number of detectable cancerous growths in a population of patients receiving a prophylactic (reatment relative Io an unlrealed control population, and/or delaying the appearance of delectable cancerous growths in a treated population versus an untreated control population, e.g., by a statistically and/or clinically significant amount.
  • Prevention of an infection includes, for example, reducing the number of diagnoses of the infection in a treated population versus an untreated control population, and/or delaying the onset of symptoms of the infection in a treated population versus an untreated control population.
  • Radiosensitizer is defined as a therapeutic agent that, upon administration in a therapeutically effective amount, promotes the treatment of one or more diseases or conditions that are treatable with electromagnetic radiation.
  • radiosensitizers are intended to be used in conjunction with electromagnetic radiation as part of a prophylactic or therapeutic treatment. Appropriate radiosensitizers to use in conjunction with treatment with the subject compositions will be known to those of skill in the art.
  • Electromagnetic radiation as used in this specification includes, but is not limited to, radiation having the wavelength of 10 ⁇ 20 to 10 meters.
  • electromagnetic radiation employ the electromagnetic radiation of: gamma-radiation (10 '2 ° to 10 ⁇ 13 m), x-ray radiation (10 "u to 10 “9 m), ultraviolet light (10 nm to 400 nm), visible light (400 nm to 700 nm), infrared radiation (700 nm to 1.0 mm), and microwave radiation (1 mm to 30 cm).
  • systemic administration means administration of a subject composition or other material at a site remote from the disease being treated.
  • Administration of an agent directly into, onto or in the vicinity of a lesion of the disease being treated, even if the agent is subsequently distributed systemically, may be termed “local” or “topical” or “regional” administration, other than directly into the central nervous system, e.g., by subcutaneous administration, such that it enters the patient's system and, thus, is subject to metabolism and other like processes.
  • a therapeutically effective amount of a therapeutic agent for in vivo use will likely depend on a number of factors, including: the rate of release of the agent from the polymer matrix, which will depend in part on the chemical and physical characteristics of the polymer; the identity of the agent; the mode and method of administration; and any other materials incorporated in the polymer matrix in addition to the agent.
  • the term "ED 50 " is art-recognized. In certain embodiments, ED 50 means the dose of a drug which produces 50% of its maximum response or effect, or alternatively, the dose which produces a pre-determined response in 50% of test subjects or preparations.
  • the term "LD 5 0" is art-recognized.
  • LDjo means the dose of a drug which is lethal in 50% of test subjects.
  • therapeutic index is an art-recognized term which refers to the therapeutic index of a drug, defined as LD 5 o/ED 50 .
  • incorporated and "encapsulated” are art-recognized when used in reference to a therapeutic agent and a polymeric composition, such as a composition disclosed herein. In certain embodiments, these terms include incorporating, formulating or otherwise including such agent into a composition which allows for sustained release of such agent in the desired application.
  • the terms may contemplate any manner by which a therapeutic agent or other material is incorporated into a polymer matrix, including for example: attached to a monomer of such polymer (by covalent or other binding interaction) and having such monomer be part of the polymerization to give a polymeric formulation, distributed throughout the polymeric matrix, appended to the surface of the polymeric matrix (by covalent or other binding interactions), encapsulated inside the polymeric matrix, etc.
  • co-incorporation or “co-encapsulation” refers to the incorporation of a therapeutic agent or other material and at least one other a therapeutic agent or other material in a subject composition.
  • a therapeutic agent or other material may be first encapsulated in a microsphere and then combined with the polymer in such a way that at least a portion of the microsphere structure is maintained.
  • a therapeutic agent or other material may be sufficiently immiscible in a controlled-release polymer that it is dispersed as small droplets, rather than being dissolved, in the polymer. Any form of encapsulation or incorporation is contemplated by the present disclosure, in so much as the sustained release of any encapsulated therapeutic agent or other material determines whether the form of encapsulation is sufficiently acceptable for any particular use.
  • biocompatible plasticizer is art-recognized, and includes materials which are soluble or dispersible in the controlled-release compositions described herein, which increase the flexibility of the polymer matrix, and which, in the amounts employed, are biocompatible.
  • Suitable plasticizers are well known in the art and include those disclosed in U.S. Patent Nos. 2,784,127 and 4,444,933.
  • plasticizers include, by way of example, acetyl tri-n-butyl citrate (c.20 weight percent or less), acetyl trihexyl citrate (c.20 weight percent or less), butyl benzyl phthalate, dibutyl phthalate, dioctylphthalate, n-butyryl tri-n-hexyl citrate, diethylene glycol dibenzoate (c. 20 weight percent or less) and the like.
  • nasal breathing assist device 1 comprises generally a pair of open ended tubular elements 10 connected together by a coupler element 16.
  • the tubular elements 10 are generally circular in cross section and extend a distance along tube axes Xl and X2 from first ends 12 to second ends 14.
  • the tubular elements taper linearly from a relatively large diameter cross section along the tube axes Xl and X2 to a relatively smaller diameter cross section from the first end 12 to the second end 14.
  • the taper may be other than linear, for example, contoured to correspond generally to the taper inside the user's nostrils.
  • First ends 12 also connect to the coupler element 16.
  • the tubular elements 10 are conic-frustums, but other shapes may be used.
  • the tubular elements could have elliptical or other shaped cross sections.
  • the inner diameter tapering monotonically from the large end to the small end, it could decrease initially, become larger, then decrease again.
  • the tubular elements 10 may also include at least one passageway 18 extending through the walls of the tubular elements transverse to the tube axes Xl and X2.
  • the passageways 18 may be circular, elliptical, or elongated at least in part in the direction of the tube axes. Alternately, the passageways can be elongated in a direction extending circumferentially around the tube axes.
  • the coupler element 16 is a resilient, nominally curved strut which maintains the tubular elements spaced apart, with axes Xl and X2 in a substantially parallel relationship, and in substantially a common plane.
  • the coupler element may be made of resilient, semi-rigid, or rigid material.
  • Grooves 19 inside of tubular elements are an additional feature which may be used to receive medication (nasal cream) before inserting in nasal passage so as not to irritate the skin inside the nasal passage, this allows the medication to be effective without contacting the nasal passage.
  • coupler element 16 maintains a nominal distance D between the tubular elements 10 that generally corresponds to the distance between the user's nostrils.
  • the coupler element extends in a plane that is essentially parallel to tube axes Xl and X2.
  • the resistance of coupler element As shown in FIGS . 3 A and 3B, the resistance of coupler element
  • Angle A can be as much as 15° or greater.
  • coupler element 16 permits relative flexing motion of the device about an axis, substantially perpendicular to the tube axes Xl and X2.
  • device 1 ' has coupler element 16' which extends between first ends 12.
  • the central axis of coupler element 16' lies in a plane that is substantially perpendicular to the tube axes Xl and
  • coupler element 16' permits relative flexing motion of device 1 ' so that axes Xl and X2 remain substantially parallel, but separation S of those axes varies to accommodate spacing of the nostrils.
  • tab supports 20 extend from first ends 12 and connect to coupler element 16.
  • Tabs 22 extend from tab supports 20 a distance M in the direction of the central axis to distal ends of the tabs.
  • Tabs 22 are preferably made of non-resiliently deformable materials, for example, metal including copper, aluminum, and etc.
  • tabs 22 may be made of the same or different materials as that used for the tabs 22.
  • tabs 22 remain outside the user's nostrils, and, acting as clips, help secure the device in the nostrils.
  • the tabs 22 also function as a stop which prevent the device from being wholly inserted into a user's nostril.
  • the tabs 22 are substantially S-shaped, and includes a distal curved portion 23 distal from the first end 12.
  • the distal curved portion 23 defines a relatively small gap G with an outer surface of the tubular element.
  • the tabs 22 are constructed such that the small gap G is adapted to receive a lateral wall of a user's nose, and the tabs 22 are adapted to clip on the lateral wall of the user's nose.
  • the tab 22 includes at least one relatively small protrusion 50 extending from the distal curved portion 23 toward the tubular element 10, as best shown in Figure. 4B and Figure. 5B.
  • the relatively small protrusion 50 extending from the distal curved portion 23 toward the tubular element 10, as best shown in Figure. 4B and Figure. 5B.
  • the tab 22 includes protrusions 50 extending from the distal curved portion 23 toward the tubular element 10, and the tubular element 10 also includes protrusions opposing to the protrusions of the tab 22.
  • the protrusions 50 extends from a distal end of the tab 22 toward the tubular element 10. The small protrusion helps to secure the device in the user's nostrils.
  • FIGS. 5A -5E show other embodiments of nasal breathing assist devices.
  • device 1 has a tubular element 10 extending along a tube axis X between a relatively large diameter first end 12 and tapering toward a relatively smaller diameter second end 14.
  • tubular element 10 may have passageways 18 extending through the walls of the tubular elements transverse to tube axis X.
  • FIG. 5C illustrates another preferred embodiment, in which the device includes a stop member 52 extending radially and outwardly from the first end 12 of the tubular element to a distal end.
  • the stop member 52 is adapted to engage with an open end of a user's nostril to prevent the device from being wholly inserted into the nostril when the device is in use.
  • FIG. 5C illustrates another preferred embodiment, in which the device includes a stop member 52 extending radially and outwardly from the first end 12 of the tubular element to a distal end.
  • the stop member 52 is adapted to engage with an open end of a user's nostril to prevent the device from being wholly inserted into the nostril when the device is in use.
  • the tab 22 has an inner surface, which faces the tubular element and is at least partially coated with adhesive 98, as shown in FIGS. 1OA and 1OB.
  • the tab 22 is also preferably non-resiliently deformable.
  • the tab 22 keeps in contact with the outer surface of the user's nose.
  • the adhesive coating increases the friction between the tab 22 and the outer surface of the user's nose, and make the tab to stick to the outer surface of the user's nose, thus increasing the stability of the device within the user's nose.
  • the adhesive coating of the inner surface of the tab helps to maintain the device within a user's nose, preventing the device from being knocked off during sleep, sports, or other activities.
  • a filter may be secured to a device in several other ways, such as by adhesive, snap-fitting, press-fitting, integral molding, twist-locking, sliding into groove(s) 19, and/or by use of hook-and-loop fasteners (such as VELCRO® brand fasteners).
  • FIG. 7 illustrates a cross-sectional view of one tubular element 10 in accordance with one preferred embodiment of the invention.
  • the protrusion 38 extends throughout an inner circumference at the first end 12 (the end with, a relatively large diameter) of the inner channel 36.
  • the filter 30 is snap-plugged into the channel 36 from the first end of the channel 36, and because the diameter of the channel 36 tapers from the first end to the second end, the filter can be secured by the inner surface of the channel 36 and the protrusion 38.
  • the protrusion 38 is relatively small, so that the filter 36 can by easily removed and replaced.
  • FIG. 8 shows a schematic view of the filters 30 together with a nasal breathing assist device.
  • Each tubular element 10 includes relatively small protrusions 38 securing the filter 30 at the first end of the tubular element 10.
  • the filter 30 is preferably positioned at one of the two ends of the tubular element 10, so that the filter 30 can be easily removed and replaced, but the filter 30 also can be positioned at a place between the two ends and secured by protrusions extending radially adjacent that place.
  • FIG. 9 illustrates another preferred embodiment of the present invention.
  • the device further includes at least one removable medication carrier 60 which may include a medium adapted to bear a therapeutic agent.
  • the removable carrier 60 preferably includes a frame tapering from a first end to a second end.
  • the frame includes two opposite edges 62.
  • the tubular element 10 further defines two opposing channels 64 on an inner surface of the tubular element 10.
  • the two opposing channels 64 extend substantially in the same direction as the central axis and are adapted to receive the two opposite edges 62 of said removable carrier 60.
  • the frame of the removable medication carrier 60 may be constructed with other shapes, and the tubular element may define corresponding channels or other mechanism for receiving the frame of the carrier 60.
  • the therapeutic agent may be medications, for example, antibiotics, for treating chronic sinusitis or other nasal diseases.
  • the filter is a liner filter (as denoted by number 80 in Figures. 1OA and 10B) including a conic-shaped liner portion 82 extending between two ends 84 and 86.
  • the relatively large end 84 is a closed end having a filter medium spanning the circumference of the end of the liner portion, and the other end 86 is an opened end.
  • the filter medium is attached to the relatively small end 86, and the relative large end is an open-faced end.
  • the liner portion 82 preferably but not necessarily, is constructed by the filter medium.
  • the filter 80 preferably but not necessarily is made from a unitary sheet of a filter medium by a molding process. The filter 80 is sized to fit in the open-faced inner channel 36 defined in the tubular clement 10.
  • the tubular clement 10 may include at least one relatively small protrusion extending radially from an inner surface of the inner channel 36 at the relatively large end of the tubular element for preventing the liner filter 80 from slipping out of the channel 36 of the tubular element 10.
  • the liner filter 80 is inserted into and retained in the inner channel 36 of the tubular element 10.
  • the liner filter 80 can be easily removed from the inner channel 36, and can be replaced or cleaned.
  • the filter medium is constructed to filter pollen, dust, mold, and/or other particles that may cause allergic reactions or other diseases or discomfort.
  • the filter medium is preferably made from a material that can be coated with medications, particularly, medications for treating nasal diseases.
  • exemplary medications include decongestants, antihistamine, and antibiotic.
  • the filters as illustrated in Figures. 6-8, the medication carriers shown in Figure. 9, and the liner filters as shown in Figures. 1OA and 1OB can be used with nasal breathing assist devices, which have one tubular element or have a pair of tubular elements connected by a strut, as described in the previous embodiments.
  • the nasal breathing assist devices can be disposable or reusable.
  • the reusable devices can be easily cleaned by rinsing, washing, or scrubbing with water, such as hot tap water, with soap and water, with isopropyl alcohol, or by steam sterilizing (such as by microwave sterilizer), autoclaving, or boiling in tap water.
  • the device can be made of rigid, semi-resilient, or resilient materials.
  • the device could include more than two stiffening rings, and/or other shape stiffening parts embedded in the conic wall of the tubular element 10.
  • the stiffening clement 90 also can be attached to the inner surface or outer surface of the tubular clement 10.
  • the stiffening element prevents the tubular element 10 from collapse when under pressure and maintain opening of the nasal passage in severe cases, for example, pathologic nasal valve collapse, septal deviation, and other types of nasal congestion or obstruction.
  • the stiffening element also increases the resilience of the tubular element 10 and the stability of the tubular element 10 within a user's nostrils.
  • the stiffening element 90 includes an elongated wire embedded within the tubular element 10 and the tab 22.
  • part of the device is made from a non-resiliently deformable material, for example, aluminum.
  • the tabs 22 shown in Figures. 4A- 5E are made from a non-resiliently deformable material.
  • an elongated metal wire is embedded within the tubular element 10 and the tab 22.
  • the wire is non-resiliently deformable, enabling the tab 22 non-resiliently deformable.
  • the wire is made from a resilient material, enabling the tab 22 resiliently deformable.
  • the user can force the tab 22 toward the outer surface of the user's nose to allow the tab 22 to touch the outer surface of the user's nose.
  • the tab 22 will stay in contact with the outer surface of the user's nose, thus preventing the device from slipping out of the user's nose.
  • at least part of the device is made from a shape memory material, such as a nickel-titanium alloy.
  • the device may have one shape under room temperature, and after the device is inserted into the user's nostrils, where the temperature is normally higher than the room temperature, the device returns to its original shape that fit the contour of the inside of the user's nostrils.
  • the device may also be coated, or embedded with medications for treating nasal diseases, or other diseases, such as skin or mucous diseases.
  • the nasal breathing assist device is inserted in the user's nostrils, as shown in FIG. 12, usually at bedtime.
  • the tubular elements maintain open nasal passages during sleeping, which allow the patient to obtain sufficient airflow through the nose only, rather than supplementing the air supply through the mouth.
  • the filters can be made to absorb or hold pollen, dust, particles in smoke and smog fumes, nicotine in tobacco smoke, obnoxious odors, and other irritating elements.
  • FIGS. 13-21 depict nasal devices embodying additional features. These additional features may or may not be combined, as desired, with features described elsewhere in this disclosure.
  • FIG. 13 depicts a device 100 having a roughly frustoconical, dome-like, or cylindrical shape.
  • the device includes a wall having a first end 12 and a second end 14.
  • the wall may define one or more passageways 18 as described previously.
  • the first and second ends define openings that allow passage of air or the positioning of insert(s), as described previously.
  • the diameter, diagonal measure, and/or cross-sectional area of the second end may be smaller than that of the first end, to facilitate positioning of the device in, for example, a nostril.
  • the first end portion of the wall defines a break 130, so that the first end opening is not completely encircled.
  • the break may be continuous with a passageway, as shown. The break may increase the flexibility of the device.
  • the second end need not define a break and may instead completely encircle the second end opening.
  • the device may also include a foot 140 protruding from the firstend.
  • the foot may protrude outward as shown in FIG. 13, downward as shown in FIG. 14, or at intermediate angles.
  • the foot may be rigidly positioned or may be flexible so that it can be positioned selectively.
  • the foot may be so formed as to permit its remaining at a selected orientation, such as by embedding a metal wire or ribbon in the foot.
  • the foot itself may be malleable to permit adjustment.
  • FIG. 15 depicts another embodiment of a device in which the second end defines a break 130, and the device includes a tab support 20.
  • the device may further include a tab (not shown), which may be used to clip the device to a subject's nose, for example.
  • FlG. 16 depicts yet another embodiment of a device in which the break 130 is positioned at some distance away from feature 150 (such, as foot 140 or lab support 20). The break may, buLneed not, be adjacent feature 150.
  • FlG. 17 depicts an embodiment of a device having more then one break 130 in the first end of the wall. Any desired number of breaks may be provided in the first end.
  • FIG. 17 also shows grooves or ribs 160, which may be thinned or thickened portions of the wall, respectively. Ribs may also be strips of material (such as metal or plastic) attached to or embedded in the wall.
  • FIG. 18 depicts an embodiment of a device in which the first end has one or more thinned or webbed portions 170. Like the breaks described previously, the thinned or webbed portions may provide the device with greater flexibility. The thinned or webbed portions may be a thinner portion of the same material as the device's wall or may be made of a different material that is either thinner than and/or is more flexible than, the material of the rest of the first end.
  • FIG. 19 depicts an embodiment of a device having attached to it a tether 180.
  • the tether may be a pull string or other appendage to facilitate positioning and/or removal of the device.
  • the tether may be a cannula, i.e., a tube that carries a fluid or gas, such as air, oxygen-enriched air, oxygen, etc.
  • a connector 200 may connect devices 100.
  • the connector may be rigid or pliable. It may be so shaped as to avoid contacting nasal tissue in order to prevent irritation or damage UJ the tissue. Alternatively, as shown in FIG. 21, there may be no connection between the devices; each device receives a cannula (or other tether).
  • devices may be given circular, elliptical, or other cross sections. This may be done to ensure that when a device is inserted into an anatomic space, such as a nostril, that space's geometry changes.
  • the device may also be made of material sufficiently stiff to overcome the anatomic space's shape. In other words, the device may be intentionally designed not to conform the anatomy but to alter it.
  • the passageways in the device act to help circulate the medication or agent within the nasal passageways by keeping the nasal passages open.
  • Possible biologically active agents include without limitation, medicaments; vitamins; mineral supplements; substances used for the treatment, prevention, diagnosis, cure or mitigation of disease or illness; substances that affect the structure or function of the body; herbal preparations; aromatherapy substances; or homeopathic substances.
  • the therapeutic agents arc used in amounts that arc therapeutically effective, which varies widely depending largely on the particular agent being used.
  • the amount of agent incorporated into the composition also depends upon the desired release profile, the concentration of the agent required for a biological effect, and the length of time that the biologically active substance has to be released for treatment.
  • the biologically active substance may be blended with a polymer matrix at different loading levels, in one embodiment at room temperature and without the need for an organic solvent.
  • the compositions may be fo ⁇ nulated as microspheres.
  • biologically active agents include, either directly or after appropriate modification, without limitation: anti-angiogenesis factors, antiinfectives such as antibiotics and antiviral agents; analgesics and analgesic combinations; anorexics; antihelmintics; antiarthritics; antiasthmatic agents; anticonvulsants; antidepressants; antidiuretic agents; antidiarrheals; antihistamines; antiinflammatory agents; antimigraine preparations; antinauseants; antineoplastics; antiparkinsonism drugs; antiproliferatives; antimitotics; antimetabolite compounds; angiostatics; angioslalic steroids;antipruritics; antipsychotics; antipyretics, antispasmodics; anticholinergics; sympatanibucil, acetriglycerin, acetamines, acetamines, acetamines, acetamines, acetamines, acetamines, acetamines, acet
  • biologically active agents include peptide, proteins or other biopolymers, e.g., interferons, interleukins, tumor necrosis factor, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4/5), ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), cholinergic differentiation factor/Leukemia inhibitory factor (CDF/LIF), epidermal growth factor (EGF), insulin-like growth factor (IGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), erythropoietin, growth hormone, Substance-P, neurotensin, insulin, erythropoietin, albumin, transferrin, and other protein biological response modifiers.
  • NTF nerve growth factor
  • BDNF brain-derived neurotrophic factor
  • NT-3 neurotrophin-3
  • NT-4/5 neurotrophin-4/5
  • CNTF
  • biologically active agents include accbutolol, acetaminophen, acctohydoxamic acid, acctophcnazinc, acyclovir, adrcnocorticoids, allopurinol, alprazolam, aluminum hydroxide, amantadine, ambenonium, amiloride, aminobenzoate potassium, amobarbital, amoxicillin, amphetamine, ampicillin, androgens, anesthetics, anticoagulants, anticonvulsants-dione type, antithyroid medicine, appetite suppressants, aspirin, atenolol, atropine, azatadine, bacampicillin, baclofen, beclomethasone, belladonna, bendroflumethiazide, benzoyl peroxide, benzthiazide, benztropine, betamethasone, betha nechol, biperiden, bisa
  • antimetabolites may be used as upon appropriate modification if necessary, including without limitation methotrexate, 5-fluorouracil, cytosine arabinoside (ara-C), 5-azacytidine, 6-mercaptopurine, 6-thioguaninc, and fludarabinc phosphate.
  • Antitumor antibiotics may include but arc not limited to doxorubicin, daunorubicin, dactinomycin, bleomycin, mitomycin C, plicamycin, idarubicin, and mitoxantrone.
  • Vinca alkaloids and epipodophyllo toxins may include, but are not limited to vincristine, vinblastine, vindesine, etoposide, and teniposide.
  • Nitrosoureas, including carmustine, lomustine, semustine and streptozocin, may also be prodrugs, upon appropriate modification if necessary.
  • Antitumor drugs that are radiation enhancers may also be used as prodrugs, upon appropriate modification if necessary.
  • biologically active agents include, for example, the chemotherapeutic agents 5'-fiuorouracil, mitomycin, cisplatin and its derivatives, taxol, bleomycins, daunomycins, and methamycins.
  • Antibiotics may be used as prodrugs as well, upon appropriate modification if necessary, and they are well known to those of skill in the art, and include, for example, penicillins, cephalosporins, tetracyclines, ampicillin, aureothicin, bacitracin, chloramphenicol, cycloserine, erythromycin, gentamicin, gramacidins, kanamycins, neomycins, streptomycins, tobramycin, and vancomycin.
  • agents upon appropriate modification if necessary, which may be used include those presently classified as investigational drugs, and can include, but are not limited to alkylating agents such as Nimustine AZQ, BZQ, cyclodisone, DADAG, CB 10-227, CY233, DABIS maleate, EDMN, Fotemustine, Hepsulfam, Hexamethylmelamine, Mafosamide, MDMS, PCNU, Spiromustine, TA-077, TCNU and Temozolomide; antimetabolites, such as acivicin, Azacytidine, 5-aza-deoxycytidine, A-TDA, Benzylidene glucose, Carbetimer, CB3717, Deazaguanine mesylate, DODOX, Doxifluridine, DUP-785, 10-ED AM, Fazarabine, Fludarabine, MZPES, MMPR, PALA, PLAC, TCAR, TMQ, TNC-P and
  • controlled-release compositions upon contact with a mucous membrane or secretions therefrom, release a therapeutic substance over a sustained or extended period (as compared to the release from an isotonic saline solution).
  • a sustained or extended period as compared to the release from an isotonic saline solution.
  • Such a system may result in prolonged delivery (over, for example, 2 to 4,000 hours, even 4 to 1500 hours) of effective amounts (e.g., 0.00001 mg/kg/hour to 10 mg/kg/ho ⁇ r) of the drug.
  • This dosage form may be administered as is necessary depending on the subject being treated, the severity of the affliction, the judgment of the prescribing physician, and the like.
  • controllcd-rclcasc compositions arc adapted for transmucosal administration.
  • anatomic area refers to an area of nasal or nasopharyngeal anatomy.
  • the pharmaceutical compositions are understood to exert their effect in part by contact with a portion of the anatomic area being treated. Contact refers to a physical touching, either directly with the subject composition being applied without intervening barrier to the anatomic area being treated, or indirectly, where the subject composition is applied to or is formed on a surface of an interposed material, passing through to come into direct contact with the anatomic area being treated.
  • composition alternatively, may be formed as a solid object implantable in the anatomic area, or as a film or mesh that may be used to cover a segment of the area.
  • a variety of techniques for implanting solid objects in relevant anatomic areas will be likewise familiar to practitioners of ordinary skill in the art.
  • sustained release devices and compositions are described in U.S. Patent Nos. 5,618,563, 5,792,753, 5,942,241, 5,985,850, 6,096,728, 6,214,387, 6,217,911, 6,248,345, 6,335,035, 6,346,519, 6,426,339, 6,428,804, 6,451,335, 6,511,958, 6,514,514, 6,514,516, 6,521,259, 6,524,606, 6,524,607, 6,527,760, 6,528,097, 6,528,107, 6,534,081, 6,565,534, 6,582,715, 6,590,059, and 6,699,471; and in U.S. Patent Application Publication Nos. US 2003/0139811 Al and US 2003/0093157 Al; and in PCT Publication No. WO/0061152 Al . AU of these documents are hereby incorporated herein by this reference.
  • the polymer composition may be a flexible or flowable material.
  • the polymer composition when the polymer used is itself flowable, the polymer composition, even when viscous, need not include a biocompatible solvent to be flowable, although trace or residual amounts of biocompatible solvents may still be present [0134J
  • a fluid polymer may be especially suitable for the transmucosal delivery of therapeutics.
  • a fluid material may be adapted for injection or instillation into a tissue mass or into an actual or potential space.
  • Certain types of fluid polymers may be termed flowable.
  • a flowable material often capable of assuming the shape of the contours of an irregular >space, may be delivered to a portion of an actual or potential space to flow therefrom into a larger portion of the space.
  • the flowable material may come to coat an entire post-operative surgical site after being inserted through an edge of an incision or after being instilled through a drain or catheter left in the surgical bed.
  • the flowable material may perform hydrodissection, thus opening up a potential space and simultaneously coating the space with polymer.
  • potential spaces suitable for hydrodissection may be found in various identifiable anatomic areas in the nose or nasopharynx.
  • a flowable polymer may be particularly adapted for instillation through a needle, catheter or other delivery device such as an endoscope, since its flowable characteristics allow it to reach surfaces that extend beyond the immediate reach of the delivery device.
  • a flowable polymer in a highly fluid state may be suitable for injection through needles or catheters into tissue masses, such as tumors or margins of resection sites.
  • Physical properties of polymers may be adjusted to achieve a desirable state of fluidity or flowability by modification of their chemical components and crosslinking, using methods familiar to practitioners of ordinary skill in the art.
  • a flexible polymer may be used in the fabrication of a solid article. Flexibility involves having the capacity to be repeatedly bent and restored to its original shape. Solid articles made from flexible polymers are adapted for placement in anatomic areas where they will encounter the motion of adjacent organs or body walls. Certain areas of motion are familiar to practitioners dealing with nasal or nasopharyngeal problems. A flexible solid article can thus be sufficiently deformed by those moving tissues that it does not cause tissue damage.
  • Solid articles may be formed as films, meshes, sheets, tubes, or any other shape appropriate to the dimensions and functional requirements of the particular anatomic area. Physical properties of polymers may be adjusted to attain a desirable degree of flexibility by modification of the chemical components and crosslinking thereof, using methods familiar to practitioners of ordinary skill in the art.
  • suitable biocompatible solvents when used, include N-methyl-2- ⁇ yrrolidone, 2-pyrrolidone, ethanol, propylene glycol, acetone, methyl acetate, ethyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, dimethyl-sulfoxide, oleic acid, or l-dodecylazacycloheptan-2-one.
  • solvents include N-methyl-2-pyrrolidone, 2-pyrrolidone, dimethyl sulfoxide, and acetone because of their solvating ability and their biocompatibility.
  • the microspheres may be manufactured by incorporating the drug into the polymer matrix by either dissolving or suspending the drug into polymer solution and the mixture will be subsequently dried by techniques familiar to those skill in the arts to form microspheres. These techniques include but not limited to spray drying, coating, various emulsion methods and supercritical fluid processing.
  • the microspheres may be mixed with a pharmaceutically acceptable diluent prior to the administration for injection. They may also be directly applied to the desired site, such as a surgical wound or cavity, by various delivery systems including pouring and spraying.
  • the microspheres may also be mixed with pharmaceutically acceptable ingredients to create ointment or cream for topical applications.
  • the subject polymers are soluble in one or more common organic solvents for ease of fabrication and processing.
  • Common organic solvents include such solvents as chloroform, dichloromethane, dichloroelhane, 2-butanone, butyl acetate, ethyl butyrate, acetone, elhyl acetate, dime thy lacetamide, N-melhyl pyrrolidone, dimethylformamide, and dimethylsulfoxide.
  • Pharmaceutically acceptable polymeric carriers may also comprise a wide range of additional materials.
  • additional materials may include diluents, binders and adhesives, lubricants, disintegrants, colorants, bulking agents, flavorings, sweeteners, and miscellaneous materials such as buffers and adsorbents, in order to prepare a particular medicated composition, with the condition that none of these additional materials will interfere with the intended purpose of the subject composition.
  • Plasticizers and stabilizing agents known in the art may be incorporated in polymers.
  • additives such as plasticizers and stabilizing agents are selected for their biocompatibility.
  • a composition may further contain one or more adjuvant substances, such as fillers, thickening agents or the like.
  • materials that serve as adjuvants may be associated with the polymer matrix.
  • additional materials may affect the characteristics of the polymer matrix that results.
  • fillers such as bovine serum albumin (BSA) or mouse scrum albumin (MSA)
  • BSA bovine serum albumin
  • MSA mouse scrum albumin
  • the amount of filler may range from about 0.1 to about 50% or more by weight of the polymer matrix, or about 2.5, 5, 10, 25, 40 percent. Incorporation of such fillers may affect the biodegradation of the polymeric material and/or the sustained release rate of any encapsulated substance.
  • Olher fillers known Io those of skill in the art such as carbohydrates, sugars, starches, saccharides, celluoses and polysaccharides, including mannitose and sucrose, may be used in certain embodiments.
  • spheronization enhancers facilitate the production of subject polymeric matrices that are generally spherical in shape.
  • Substances such as zein, microciystalline cellulose or microcrystalline cellulose co-processed with sodium carboxymethyl cellulose may confer plasticity to the subject compositions as wen as implant strength and integrity.
  • extrudates that are rigid, but not plastic result in the formation of dumbbell shaped implants and/or a high proportion of fines, and extrudates that are plastic, but not rigid, tend to agglomerate and form excessively large implants.
  • a balance between rigidity and plasticity is desirable.
  • the percent of spheronization enhancer in a formulation depends on the other excipient characteristics and is typically in the range of 10-90% (w/w).
  • Disintegrants are substances which, in the presence of liquid, promote the disruption of the subject compositions. Disintegrants are most often used in implants, in which the junction of the disintegrant is to counteract or neutralize the effect of any binding materials used in the subject formulation. In general, the mechanism of disintegration involves moisture absorption and swelling by an insoluble material. Examples of disintegrants include croscarmellose sodium and crospovidone that, in certain embodiments, may be incorporated into the polymeric matrices in the range of about 1-20% of total matrix weight. In other cases, soluble fillers such as sugars (mannitol and lactose) may also be added to facilitate disintegration of the subject compositions upon use.
  • soluble fillers such as sugars (mannitol and lactose) may also be added to facilitate disintegration of the subject compositions upon use.
  • a pore-forming agent may be added to generate additional pores in the matrix.
  • Any biocompatible water-soluble material may be used as the pore-forming agent. They may be capable of dissolving, diffusing or dispersing out of the formed polymer system whereupon pores and microporous channels are generated in the system.
  • the amount of pore-forming agent (and size of dispersed particles of such pore-forming agent, if appropriate) within the composition should affect the size and number of the pores in the polymer system.
  • Pore-forming agents include any pharmaceutically acceptable organic or inorganic substance that is substantially miscible in water and body fluids and will dissipate from the forming and formed matrix into aqueous medium or body fluids or water-immiscible substances that rapidly degrade to water-soluble substances.
  • Suitable pore-forming agents include, for example, sugars such, as sucrose and dextrose, salts such as sodium chloride and sodium carbonate, and polymers such as hydroxylpropylcellulose, carboxymethylcellulose, polyethylene glycol, and polyvinylpyrrolidone. The size and extent of the pores may be varied over a wide range by changing the molecular weight and percentage of pore-forming agent incorporated into the polymer system.
  • the charge, lipophilicity or hydrophilicity of any subject polymeric matrix may be modified by attaching in some fashion an appropriate compound to the surface of the matrix.
  • surfactants may be used to enhance wettability of poorly soluble or hydrophobic compositions.
  • suitable surfactants include dextran, polysorbates and sodium lauryl sulfate.
  • surfactants are used in low concentrations, generally less ihan about 5%.
  • Binders are adhesive materials that may be incorporated in polymeric formulations to bind and maintain matrix integrity. Binders may be added as dry powder or as solution. Sugars and natural and synthetic polymers may act as binders. Materials added specifically as binders are generally included in the range of about 0.5%-15% w/w of the matrix formulation. Certain materials, such, as microcrystalline cellulose, also used as a spheronization enhancer, also have additional binding properties.
  • Various coatings may be applied to modify the properties of the matrices.
  • Three exemplary types of coatings are seal, gloss and enteric coatings. Other types of coatings having various dissolution or erosion properties may be used to further modify subject matrices behavior, and such coatings are readily known to one of ordinary skill in the art.
  • the seal coat may prevent excess moisture uptake by the matrices during the application of aqueous based enteric coatings.
  • the gloss coat generally improves the handling of the finished matrices. Water-soluble materials such, as hydroxypropyl cellulose may be used to seal coat and gloss coat implants. The seal coat and gloss coat are generally sprayed onto the matrices until an increase in weight between about 0.5% and about 5%, often about 1% for a seal coat and about 3% for a gloss coat, has been obtained.
  • Enteric coatings may include polymers which are insoluble in the low pH (less than 3.0) of the stomach, but are soluble in the elevated pH (greater than 4.0) of the small intestine.
  • Polymers such as EUDRAGIT, RohmTech, Inc., Maiden, Mass., and AQUATERlC, FMC Corp., Philadelphia, Perm., may be used and are layered as thin membranes onto the implants from aqueous solution or suspension or by a spray drying method.
  • the enteric coat is generally sprayed to a weight increase of about one to about 30%, or about 10 to about 15% and may contain coating adjuvants such as plasticizers, surfactants, separating agents that reduce the tackiness of the implants during coating, and coating permeability adjusters.
  • the present compositions may additionally contain one or more optional additives such as fibrous reinforcement, colorants, perfumes, rubber modifiers, modifying agents, etc.
  • each of these optional additives should be compatible with the resulting polymer and its intended use.
  • suitable fibrous reinforcement include PGA microfibrils, collagen microfibrils, cellulosic microfibrils, and olefinic microfibrils.
  • the amount of each of these optional additives employed in the composition is an amount necessary to achieve the desired effect.
  • the subject polymers may be formed in a variety of shapes.
  • subject polymer matrices may be presented in the form of microparticles or nanoparticles. Such particles may be prepared by a variety of methods known in the art, including for example, solvent evaporation, spray-drying or double emulsion methods.
  • microparticles and nanoparticles may be determined by scanning electron microscopy. Spherically shaped nanoparticles are used in certain embodiments for circulation through the bloodstream. If desired, the particles may be fabricated using known techniques into other shapes that arc more useful for a specific application. [0158] In addition to intracellular delivery of a therapeutic agent, it also possible that particles of the subject compositions, such as microparticles or nanoparticles, may undergo cndocytosis, thereby obtaining access to the cell. The frequency of such an endocytosis process will likely depend on the size of any particle.
  • solid articles useful in defining shape and providing rigidity and structural strength to the polymeric matrices may be used.
  • a polymer may be formed on a mesh or other weave for implantation.
  • a polymer may also be fabricated as a stent or as a shunt, adapted for holding open areas within body tissues or for draining fluid from one body cavity or body lumen into another.
  • a polymer may be fabricated as a drain or a tube suitable for removing fluid from a post-operative site, and in some embodiments adaptable for use with closed section drainage systems such as Jackson-Pratt drains and the like familiar in the art.
  • the mechanical properties of the polymer may be important for the processability of making molded or pressed articles for implantation.
  • the glass transition temperature may vary widely but must be sufficiently lower than the temperature of decomposition to accommodate conventional fabrication techniques, such as compression molding, extrusion or injection molding.
  • the polymers and blends upon contact with body fluids, undergo gradual degradation.
  • the life of a biodegradable polymer in vivo depends, among other things, upon its molecular weight, crystallinity, biostability, and the degree of crosslinking. In general, the greater the molecular weight, the higher the degree of crystallinity, and the greater the biostability, the slower biodcgradation will be.
  • a subject polymer matrix is formulated with a therapeutic agent, release of such an agent for a sustained or extended period as compared to the release from an isotonic saline solution generally results.
  • Such release profile may result in prolonged delivery (over, say 1 to about 4,000 hours, or alternatively about 4 to about 1500 hours) of effective amounts (e.g., about 0.00001 mg/kg/hourto about 10 mg/kg/hour) of the agent associated with the polymer.
  • effective amounts e.g., about 0.00001 mg/kg/hourto about 10 mg/kg/hour
  • a variety of factors may affect the desired rate of hydrolysis of polymers, the desired softness and flexibility of the resulting solid matrix, rate and extent of bioactive material release.
  • Some of such factors include: the selection of the various substituent groups, such as the phosphate group making up the linkage in the polymer backbone (or analogs thereof), the enantiomeric or diastereomeric purity of the monomeric subunits, homogeneity of subunits found in the polymer, and the length of the polymer.
  • the present disclosure contemplates heteropolymers with varying linkages, and/or the inclusion of other monomeric elements in the polymer, in order to control, for example, the rate of biodegradation of the matrix.
  • the release rates of different polymer systems may be compared by subjecting them to such a protocol. In certain instances, it may be necessary to process polymeric systems in the same fashion to allow direct and relatively accurate comparisons of different systems to be made. Such comparisons may indicate that any one polymeric system releases incorporated material at a rate from about 2 or less to about 1000 or more times faster than another polymeric system. Alternatively, a comparison may reveal a rate difference of about 3, 5, 7, 10, 25, 50, 100, 250, 500 or 750. Even higher rate differences are contemplated by the present disclosure and release rate protocols. [0167] In certain embodiments, when formulated in a certain manner, the release rate for polymer systems may present as mono- or bi-phasic.
  • the release rate of any incorporated material may also be characterized by the amount of such material released per day per mg of polymer matrix.
  • the release rate may vary from about 1 ng or less of any incorporated material per day per mg of polymeric system to about 5000 or more ng/day.mg.
  • the release rate may be about 10, 25, 50, 75, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800 or 900 ng/day.mg.
  • lhe release rate of any incorporated material may be 10,000 ng/day.mg or even higher.
  • materials incorporated and characterized by such release rate protocols may include therapeutic agents, fillers, and other substances.
  • the agent or substance may be dissolved to form a homogeneous solution of reasonably constant concentration in the polymer composition, or it may be dispersed to form a suspension or dispersion within the polymer composition at a desired level of "loading" (grams of biologically active substance per grams of total composition including the biologically active substance, usually expressed as a percentage).
  • a polymer composition useful in the treatment of pain, inflammation, infection, or other problems includes both: (a) a therapeutic agent, and (b) a biocompatible and optionally biodegradable polymer, such as one having the recurring monomelic units shown in one of the foregoing formulas, or any other biocompatible polymer mentioned above or known in the art.
  • the agent is an analgesic or anesthetic; for inflammation, a steroidal or non-steroidal antiinflammatory agent; and for infection, an antimicrobial effective against the pathogen(s) of concern, such as an antibiotic, antifungal, antimycotic, antimalarial, antimycobacterial, antiparasitic, or antiviral.
  • the subject compositions encapsulate more than one agenl for treatment of one or more problems.
  • a delivery system for a transmucosal therapeutic agent consists of a dispersion of such an agent into one of the polymers described above.
  • an article is used for implantatioTi, injection, or otherwise placed totally or partially within the body, the article comprising a therapeutic composition for transmucosal delivery. It may be particularly important that such an article result in minimal tissue irritation when applied to, implanted in or injected into vascularized tissue, hypovascularized tissue, post-operative tissue or tissue exposed to previous radiation that is part of the nose or nasopharynx.
  • a solid, flowable or fluid article is inserted within an anatomic area by implantation, injection, endoscopy or otherwise being placed within the anatomic area of the subject being treated.
  • the polymer compositions provide a wide variety of physical forms having specific chemical, physical and mechanical properties suitable for insertion into an anatomic area.
  • Biocompatible delivery systems and articles thereof may be prepared in a variety of ways known in the art.
  • the subject polymer may be melt processed using conventional extrusion or injection molding techniques, or these products may be prepared by dissolving in an appropriate solvent, followed by formation of the device, and subsequent removal of the solvent by evaporation or extraction, e.g., by spray drying.
  • the polymers may be formed into articles of almost any size or shape desired, for example, implantable solid discs or wafers or injectable rods, microspheres, or other microparticles.
  • Typical medical articles also include such as implants as laminates for degradable fabric or coatings to be placed on other implant devices.
  • a therapeutic formulation may be selected so that inhalation causes dislodgment or vaporization of a therapeutic into the patient's airsteam for delivery deeper in the airway (for example, in the brachial tree and/or alveoli).
  • certain polymer compositions may be used to form a soft, drug-delivery "depot" that can be administered as a liquid, for example, by injection, but which remains sufficiently viscous to maintain the drug within the localized area around the injection site.
  • the polymer composition When the polymer composition is flexible or fiowable, it may be placed anywhere within the body, including into an anatomic area. It may be inserted into the anatomic area either through an open surgical wound, under direct or indirect vision, or through any of the access devices routinely used in the art to enter such areas, for example, indwelling or acutely-inserted catheters, needles, drains, supcrsclcctivc angiography means and the like.
  • a fiowable or fluid polymer may be adapted for mixing with the transudate or exudate found within or expected to gather within the anatomic area.
  • a fiowable or fluid polymer may be instilled in an anatomic area during surgery on organs or structures therein to decrease the likelihood of recurrent disease when there is a high risk for its development.
  • a polymer composition may also be incorporated in access devices so that a therapeutic agent is released Mo the analomic area within which the access device resides.
  • the polymer composition may also be used to produce coalings for other solid implantable devices for treatment.
  • a system or implant article Once a system or implant article is in place, it should remain in at least partial contact with a biological fluid, such as blood, tissue fluid, lymph, or secretions from organ surfaces or mucous membranes, and the like to allow for sustained release of any encapsulated therapeutic agent, e.g., a therapeutic agent.
  • a biological fluid such as blood, tissue fluid, lymph, or secretions from organ surfaces or mucous membranes, and the like to allow for sustained release of any encapsulated therapeutic agent, e.g., a therapeutic agent.
  • the various nasal dilators, stents, and other devices may be combined with other forms of therapy to provide multi-modality treatments.
  • a person with a nasal or upper airway disorder may be treated by any combination of a nasal device disclosed herein and a course of antibiotics (by any route of administration), nasal sprays, and/or nasal irrigators.
  • Disorders that may especially amenable to such multi-modality treatment include upper airway allergies, congestion, rhinitis, and sinus infections.
  • the devices disclosed herein may also be used to reduce or eliminate nasal stenosis and/or scarring following nasal surgery such as septoplasty or rhinoplasty.
  • a device or devices may be positioned in one or both nostrils following surgery to help hold (lie nostril in an opened structure.
  • the device(s) can also prevent contact between surgical surface to prevent formation of adhesions or scar tissue.
  • the device(s) may be employed temporarily or permanently. They may be positioned as a step of a surgical procedure or in an out-patient setting. They may be used as a preventive measure before any postsurgical signs or symptoms occur, or as a remedial measure after an abnormal healing shape, scarring, or adhesions are observed.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pulmonology (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Otolaryngology (AREA)
  • Emergency Medicine (AREA)
  • Nursing (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Vascular Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Business, Economics & Management (AREA)
  • Emergency Management (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
EP06840036.5A 2005-11-30 2006-11-28 Nasenverstopfung, obstruktionslinderung und arzneiabgabe Active EP1968684B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US11/290,047 US8403954B2 (en) 2001-05-22 2005-11-30 Nasal congestion, obstruction relief, and drug delivery
PCT/US2006/061280 WO2007065083A2 (en) 2005-11-30 2006-11-28 Nasal congestion, obstruction relief, and drug delivery

Publications (3)

Publication Number Publication Date
EP1968684A2 true EP1968684A2 (de) 2008-09-17
EP1968684A4 EP1968684A4 (de) 2009-12-02
EP1968684B1 EP1968684B1 (de) 2016-02-24

Family

ID=38092928

Family Applications (1)

Application Number Title Priority Date Filing Date
EP06840036.5A Active EP1968684B1 (de) 2005-11-30 2006-11-28 Nasenverstopfung, obstruktionslinderung und arzneiabgabe

Country Status (6)

Country Link
US (4) US8403954B2 (de)
EP (1) EP1968684B1 (de)
CN (1) CN101616708B (de)
AU (1) AU2006320231A1 (de)
CA (2) CA2635738C (de)
WO (1) WO2007065083A2 (de)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USD753821S1 (en) 2014-06-20 2016-04-12 Asap Breatheassist Pty Ltd Nasal dilator device
USD754851S1 (en) 2014-06-20 2016-04-26 Asap Breatheassist Pty Ltd Nasal dilator device
USD754850S1 (en) 2014-06-20 2016-04-26 Asap Breatheassist Pty Ltd Nasal dilator device
USD759239S1 (en) 2013-12-06 2016-06-14 Asap Breatheassist Pty Ltd Nasal dilator device
USD774648S1 (en) 2013-07-18 2016-12-20 Asap Breatheassist Pty Ltd Nasal dilator device
RU195387U1 (ru) * 2019-12-05 2020-01-24 Общество с ограниченной ответственностью Компания "Динамика" Ингалятор для носа
US11259908B2 (en) 2016-07-20 2022-03-01 Elanco Us Inc. Animal intranasal administration device, systems, and associated methods
USD952141S1 (en) 2019-06-13 2022-05-17 Asap Breatheassist Pty Ltd Nasal dilator device

Families Citing this family (143)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001095786A2 (en) * 2000-06-16 2001-12-20 Rajiv Doshi Methods and devices for improving breathing in patients with pulmonary disease
DE10105592A1 (de) 2001-02-06 2002-08-08 Achim Goepferich Platzhalter zur Arzneistofffreigabe in der Stirnhöhle
US9242080B2 (en) * 2001-05-22 2016-01-26 Sanostec Corp Nasal inserts
US8403954B2 (en) 2001-05-22 2013-03-26 Sanostec Corp. Nasal congestion, obstruction relief, and drug delivery
US7390331B2 (en) 2001-05-22 2008-06-24 Sanostec Corp Nasal inserts
US8317816B2 (en) 2002-09-30 2012-11-27 Acclarent, Inc. Balloon catheters and methods for treating paranasal sinuses
US20070208252A1 (en) 2004-04-21 2007-09-06 Acclarent, Inc. Systems and methods for performing image guided procedures within the ear, nose, throat and paranasal sinuses
US7361168B2 (en) 2004-04-21 2008-04-22 Acclarent, Inc. Implantable device and methods for delivering drugs and other substances to treat sinusitis and other disorders
US8414473B2 (en) 2004-04-21 2013-04-09 Acclarent, Inc. Methods and apparatus for treating disorders of the ear nose and throat
US7419497B2 (en) 2004-04-21 2008-09-02 Acclarent, Inc. Methods for treating ethmoid disease
US9554691B2 (en) 2004-04-21 2017-01-31 Acclarent, Inc. Endoscopic methods and devices for transnasal procedures
US8146400B2 (en) 2004-04-21 2012-04-03 Acclarent, Inc. Endoscopic methods and devices for transnasal procedures
US20060004323A1 (en) 2004-04-21 2006-01-05 Exploramed Nc1, Inc. Apparatus and methods for dilating and modifying ostia of paranasal sinuses and other intranasal or paranasal structures
US20190314620A1 (en) 2004-04-21 2019-10-17 Acclarent, Inc. Apparatus and methods for dilating and modifying ostia of paranasal sinuses and other intranasal or paranasal structures
US8702626B1 (en) 2004-04-21 2014-04-22 Acclarent, Inc. Guidewires for performing image guided procedures
US9089258B2 (en) 2004-04-21 2015-07-28 Acclarent, Inc. Endoscopic methods and devices for transnasal procedures
US8747389B2 (en) 2004-04-21 2014-06-10 Acclarent, Inc. Systems for treating disorders of the ear, nose and throat
US7462175B2 (en) 2004-04-21 2008-12-09 Acclarent, Inc. Devices, systems and methods for treating disorders of the ear, nose and throat
US9399121B2 (en) 2004-04-21 2016-07-26 Acclarent, Inc. Systems and methods for transnasal dilation of passageways in the ear, nose or throat
US8764729B2 (en) 2004-04-21 2014-07-01 Acclarent, Inc. Frontal sinus spacer
US7410480B2 (en) 2004-04-21 2008-08-12 Acclarent, Inc. Devices and methods for delivering therapeutic substances for the treatment of sinusitis and other disorders
US8932276B1 (en) 2004-04-21 2015-01-13 Acclarent, Inc. Shapeable guide catheters and related methods
US9101384B2 (en) 2004-04-21 2015-08-11 Acclarent, Inc. Devices, systems and methods for diagnosing and treating sinusitis and other disorders of the ears, Nose and/or throat
US9351750B2 (en) 2004-04-21 2016-05-31 Acclarent, Inc. Devices and methods for treating maxillary sinus disease
US7559925B2 (en) 2006-09-15 2009-07-14 Acclarent Inc. Methods and devices for facilitating visualization in a surgical environment
US7654997B2 (en) 2004-04-21 2010-02-02 Acclarent, Inc. Devices, systems and methods for diagnosing and treating sinusitus and other disorders of the ears, nose and/or throat
US20070167682A1 (en) 2004-04-21 2007-07-19 Acclarent, Inc. Endoscopic methods and devices for transnasal procedures
US7803150B2 (en) 2004-04-21 2010-09-28 Acclarent, Inc. Devices, systems and methods useable for treating sinusitis
US10188413B1 (en) 2004-04-21 2019-01-29 Acclarent, Inc. Deflectable guide catheters and related methods
US20060063973A1 (en) 2004-04-21 2006-03-23 Acclarent, Inc. Methods and apparatus for treating disorders of the ear, nose and throat
US8894614B2 (en) 2004-04-21 2014-11-25 Acclarent, Inc. Devices, systems and methods useable for treating frontal sinusitis
CA2589922A1 (en) * 2004-12-08 2006-06-15 Ventus Medical, Inc. Respiratory devices and methods of use
US10610228B2 (en) 2004-12-08 2020-04-07 Theravent, Inc. Passive nasal peep devices
US8061357B2 (en) 2004-12-08 2011-11-22 Ventus Medical, Inc. Adhesive nasal respiratory devices
US9833354B2 (en) 2004-12-08 2017-12-05 Theravent, Inc. Nasal respiratory devices
US8951225B2 (en) 2005-06-10 2015-02-10 Acclarent, Inc. Catheters with non-removable guide members useable for treatment of sinusitis
US8114113B2 (en) 2005-09-23 2012-02-14 Acclarent, Inc. Multi-conduit balloon catheter
US8190389B2 (en) 2006-05-17 2012-05-29 Acclarent, Inc. Adapter for attaching electromagnetic image guidance components to a medical device
GB0610171D0 (en) 2006-05-23 2006-06-28 Robitaille Jean Pierre Valved nasal canula
CA2653139C (en) * 2006-05-23 2016-01-05 Ventus Medical, Inc. Nasal respiratory devices
CN101489630B (zh) 2006-06-07 2013-10-23 温吐斯医学公司 分层鼻装置
CA2658966A1 (en) * 2006-06-07 2007-12-21 Ventus Medical, Inc. Layered nasal devices
AU2007289078A1 (en) 2006-08-30 2008-03-06 David William Smith Method of imparting a mono-axial or multiaxial stiffness to extruded materials and products resulting therefrom
US9820688B2 (en) 2006-09-15 2017-11-21 Acclarent, Inc. Sinus illumination lightwire device
US7780730B2 (en) 2006-09-25 2010-08-24 Iyad Saidi Nasal implant introduced through a non-surgical injection technique
US20080097517A1 (en) 2006-10-23 2008-04-24 Webtec Converting, Llc. External Nasal Dilator and Methods of Manufacture
US8240309B2 (en) * 2006-11-16 2012-08-14 Ventus Medical, Inc. Adjustable nasal devices
US8439687B1 (en) 2006-12-29 2013-05-14 Acclarent, Inc. Apparatus and method for simulated insertion and positioning of guidewares and other interventional devices
US8667964B2 (en) * 2007-02-16 2014-03-11 Ric Investments, Llc Nasal interface
TW200836781A (en) * 2007-03-07 2008-09-16 Ventus Medical Inc Nasal devices
WO2008124787A2 (en) * 2007-04-09 2008-10-16 Acclarent, Inc. Ethmoidotomy system and implantable spacer devices having therapeutic substance delivery capability for treatment of paranasal sinusitis
US8118757B2 (en) 2007-04-30 2012-02-21 Acclarent, Inc. Methods and devices for ostium measurement
US8485199B2 (en) 2007-05-08 2013-07-16 Acclarent, Inc. Methods and devices for protecting nasal turbinate during surgery
US20090099062A1 (en) * 2007-05-31 2009-04-16 Ethan Lee Pyrvinium For The Treatment of Cancer
US20090010991A1 (en) * 2007-07-07 2009-01-08 Julian Prabhu Nasal Passage Stent
US8020700B2 (en) 2007-12-05 2011-09-20 Ventus Medical, Inc. Packaging and dispensing nasal devices
WO2009076290A2 (en) * 2007-12-06 2009-06-18 Ventus Medical, Inc. Delayed resistance nasal devices and methods of use
US8834512B1 (en) * 2007-12-12 2014-09-16 International Patent Development Group, Llc Nasal dilator comprising joined legs with end pads and air passages
DK2231065T3 (da) 2007-12-18 2021-02-01 Intersect Ent Inc Selvekspanderende anordninger
US10206821B2 (en) 2007-12-20 2019-02-19 Acclarent, Inc. Eustachian tube dilation balloon with ventilation path
US8182432B2 (en) 2008-03-10 2012-05-22 Acclarent, Inc. Corewire design and construction for medical devices
US20100211181A1 (en) * 2008-06-02 2010-08-19 Julian Prabhu Nasal passage stent
US20090308398A1 (en) * 2008-06-16 2009-12-17 Arthur Ferdinand Adjustable resistance nasal devices
NL2001698C2 (en) 2008-06-18 2009-12-22 Nasophlex B V Cardioverter / defibrillator.
WO2010014799A1 (en) 2008-07-30 2010-02-04 Acclarent, Inc. Paranasal ostium finder devices and methods
EP2184036A1 (de) * 2008-11-10 2010-05-12 Göksel Seyrek Nasenimplantat
WO2010059586A1 (en) 2008-11-19 2010-05-27 Entrigue Surgical, Inc. Apparatus and methods for correcting nasal valve collapse
ITVR20090007A1 (it) * 2009-02-04 2010-08-05 Carlo Rasconi "inserto nasale"
US20100241155A1 (en) 2009-03-20 2010-09-23 Acclarent, Inc. Guide system with suction
US7978742B1 (en) 2010-03-24 2011-07-12 Corning Incorporated Methods for operating diode lasers
US8435290B2 (en) 2009-03-31 2013-05-07 Acclarent, Inc. System and method for treatment of non-ventilating middle ear by providing a gas pathway through the nasopharynx
EP3103502A1 (de) 2009-05-15 2016-12-14 Intersect ENT, Inc. Expandierbare vorrichtungen und verfahren dafür
ITMC20090127A1 (it) * 2009-05-22 2010-11-23 Costantino Giovagnini Molla nasale per inalare sostanze e/o migliorare la respirazione
US9381332B2 (en) * 2009-10-30 2016-07-05 Brian Judd Nasal dilator
JP5061325B2 (ja) * 2010-03-05 2012-10-31 セブン ドリーマーズ ラボラトリーズ，インコーポレイテッド 咽頭部拡張用デバイス
US8875711B2 (en) 2010-05-27 2014-11-04 Theravent, Inc. Layered nasal respiratory devices
SE535611C2 (sv) 2010-06-24 2012-10-16 Nose Option Ab Näsplugg
US20120071913A1 (en) * 2010-09-21 2012-03-22 Tamez Oscar A Nasal splints
US9155492B2 (en) 2010-09-24 2015-10-13 Acclarent, Inc. Sinus illumination lightwire device
RU2532285C2 (ru) * 2011-04-27 2014-11-10 Общество с ограниченной ответственностью "ЭНДОМЕДИУМ +" Способ промывания полости носа, околоносовых полостей и носоглотки
US20130144325A1 (en) * 2011-06-02 2013-06-06 Ludwig A. Allegra Nasal dilator
EP2760390B1 (de) 2011-09-29 2019-06-12 Trudell Medical International Nasaleinsatz
US20130096552A1 (en) * 2011-10-14 2013-04-18 Christopher L. Brace Hydrodissection Material with Reduced Migration
US9004071B2 (en) * 2011-10-18 2015-04-14 Ian Joseph Alexander Nasal guide and method of use thereof
US20130255680A1 (en) * 2012-03-27 2013-10-03 George Volgyesi Nasal Insert Impreganted with an Aromatherapy Oil
DE102012223691A1 (de) * 2012-12-19 2014-06-26 Heine Optotechnik Gmbh & Co Kg Otoskop mit abwerfbarem Ohrtrichter
WO2014134303A1 (en) 2013-02-27 2014-09-04 Spirox, Inc. Nasal implants and systems and methods of use
US9433437B2 (en) 2013-03-15 2016-09-06 Acclarent, Inc. Apparatus and method for treatment of ethmoid sinusitis
US9629684B2 (en) 2013-03-15 2017-04-25 Acclarent, Inc. Apparatus and method for treatment of ethmoid sinusitis
EP3010576B1 (de) * 2013-06-18 2018-11-28 Cornell University Führung zur nasensprayverabreichung
US20150005806A1 (en) 2013-07-01 2015-01-01 Variety Children's Hospital d/b/a Miami Children's Hospital, Inc. Rhinoplasty appliance and method of forming the same
US8998986B1 (en) * 2013-07-05 2015-04-07 Zdzislaw B. Malinowski Nasal stent
US9585601B2 (en) * 2013-08-15 2017-03-07 Chunyuan Qiu Systems, methods and devices for diagnosing sleep apnea
NL1040380C2 (en) * 2013-09-07 2015-03-10 Anthonius Fredericus Maria Bende Face masks and software/application for activating no production in sinuses.
US20160256716A1 (en) * 2013-10-17 2016-09-08 Wang Lei Nasal filter
USD738497S1 (en) * 2013-11-15 2015-09-08 Joel Jackson Bell-shaped nasal dilator
FR3016123B1 (fr) * 2014-01-03 2016-02-05 Georges Creps Dispositif nasal ambulatoire ameliore
US10569037B2 (en) * 2014-02-14 2020-02-25 John M. O'Day Nasopharyngeal device for obstructive sleep apnea syndrome
US9782289B1 (en) * 2014-03-21 2017-10-10 Farhoud Z. Rastegar Sinus passage expansion device
USD746468S1 (en) 2014-04-22 2015-12-29 Snorebuds, Llc Nasal insert
USD737965S1 (en) * 2014-04-23 2015-09-01 Anthonius Fredericus Maria Bende Nasal dilator
KR101573322B1 (ko) * 2014-05-29 2015-12-02 메디코코(주) 유연한 중공체를 가진 비강 호흡량 증가 장치
US11712361B2 (en) 2014-06-20 2023-08-01 Asap Breatheassist Pty Ltd Nasal dilator devices
US10398545B2 (en) 2014-08-26 2019-09-03 Spirox, Inc. Nasal implants and systems and method of use
AU360484S (en) 2015-01-30 2015-02-26 Asap Breatheassist Pty Ltd Nasal dilator device
US10195088B2 (en) 2015-04-13 2019-02-05 Emergency Medical Innovation LLC Nasal compression device
EA034930B1 (ru) * 2015-06-05 2020-04-08 ЭЙСЕП БРИТЭССИСТ ПиТиАй ЭлТэДэ Носовой расширитель
AU363373S (en) 2015-06-05 2015-08-12 Asap Breatheassist Pty Ltd Nasal dilator device
JP2018523512A (ja) 2015-07-31 2018-08-23 エーエスエーピー ブレスアシスト ピーティーワイ リミテッド 鼻孔装置
DE202015006433U1 (de) * 2015-09-08 2015-09-23 Michael Zisser Kompakter Zerstäuber zur Inhalation von flüchtigen Wirkstoffen
WO2017053824A1 (en) 2015-09-25 2017-03-30 Spirox, Inc. Nasal implants and systems and method of use
AU366601S (en) 2015-12-24 2016-01-15 Asap Breatheassist Pty Ltd Nasal dilator device
EP3207868A1 (de) 2016-02-19 2017-08-23 Patonomics AB Verfahren und vorrichtung zur identifizierung eines vorübergehenden emotionalen zustands eines lebenden säugers
WO2017165583A1 (en) * 2016-03-23 2017-09-28 Sanostec Corp Nasal insert having one or more sensors
WO2017192394A1 (en) 2016-05-02 2017-11-09 Entellus Medical, Inc. Nasal valve implants and methods of implanting the same
USD789541S1 (en) * 2016-06-24 2017-06-13 Nose Budz LLC Nasal air purifier
WO2018105131A1 (ja) * 2016-12-09 2018-06-14 Ｄｒ．Ｃ医薬株式会社 医薬製剤及び医療器具
JP6558392B2 (ja) * 2017-04-04 2019-08-14 ニプロ株式会社 シリンジ型噴出装置
EP3609432B1 (de) 2017-04-13 2024-05-22 Spirox, Inc. Nasenimplantate
CN108721761A (zh) * 2017-04-18 2018-11-02 郭明哲 鼻腔内软管
SE542541C2 (en) * 2017-05-12 2020-06-02 Noseoption Ab Nasal device
CN111699015B (zh) * 2017-12-05 2024-03-15 新加坡科技研究局 呼吸系统分泌物管理系统
CN108421138A (zh) * 2017-12-25 2018-08-21 宫本海 一种鼻腔雾化吸药器
US11147735B2 (en) 2018-02-26 2021-10-19 Olympic Ophthalmics, Inc. Therapeutic handheld devices for disorders
CN109806041A (zh) * 2018-04-26 2019-05-28 北京大学第三医院 前鼻孔支架
TWI660756B (zh) * 2018-05-22 2019-06-01 蔡淑真 Nasal inserter
US11141611B2 (en) * 2018-06-12 2021-10-12 Faith Jones Filter tube respirator
FR3086531B1 (fr) * 2018-10-01 2020-10-30 Bone 3D Conformateur narinaire
KR102010191B1 (ko) * 2018-10-19 2019-08-12 이형주 코골이 방지용 비강 확장구
CN109498947B (zh) * 2018-12-24 2021-05-04 青岛市城阳区人民医院 一种呼吸科患者用防鼾通气面罩
CN109464733B (zh) * 2018-12-28 2020-05-22 深圳市稳利科技有限公司 鼻炎护理装置
US11523928B2 (en) * 2019-01-25 2022-12-13 College Of Medicine Of King Khalid University Choanal atresia apparatus
CN117503461A (zh) * 2019-01-25 2024-02-06 迅息Pty有限公司 鼻用装置的外壳以及相应的方法
KR102108490B1 (ko) * 2019-05-14 2020-05-08 박균섭 코 삽입형 약성 물질 공급 장치
US11235184B1 (en) * 2019-05-30 2022-02-01 Gregory Gary Caputy Intranasal cannula apparatus for filtering air
US11793957B2 (en) 2019-08-20 2023-10-24 Vasu Sharma Apparatus and method for manipulating characteristics of inhaled air
US20220378598A1 (en) 2019-11-04 2022-12-01 Regents Of The University Of Michigan Nasopharyngeal Airway Devices
US11918502B2 (en) 2020-04-02 2024-03-05 Peter Catalano Bi-flow nasal stent
NL2026058B1 (en) * 2020-07-15 2022-03-18 Water & Minerals Advice B V Nose insert
IT202000022144A1 (it) * 2020-09-18 2022-03-18 FKS Holding Srl Dispositivo equilibratore nasale
CN112263794A (zh) * 2020-10-27 2021-01-26 何翰禹 具有过滤组件的鼻塞结构
US20220280817A1 (en) * 2021-03-02 2022-09-08 Fulton Carson Nostril Wearable Filtering Device
WO2024137239A1 (en) * 2022-12-23 2024-06-27 Ps Devices, Llc Nasal stent

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11192251A (ja) * 1997-12-29 1999-07-21 Hidetoshi Araki イビキの防止方法及び防止器
WO2004026391A1 (en) * 2002-09-18 2004-04-01 Asap Breathe Assist Pty Ltd A nasal cavity dilator
US20050021073A1 (en) * 2001-05-22 2005-01-27 Ernest Santin Nasal congestion and obstruction relief and breathing assist devices

Family Cites Families (123)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US753133A (en) 1904-02-23 Inhaler
US1322375A (en) 1919-11-18 Wui kong tjn
US1311461A (en) 1919-07-29 Inhales ob
US682123A (en) 1900-08-07 1901-09-03 William Rolla Wilson Hay-fever disk.
US810617A (en) 1905-01-03 1906-01-23 Thomas Carence Nasal shield.
US878223A (en) 1906-11-28 1908-02-04 A F Meisselbach & Brother Inhaler.
US888869A (en) 1908-01-04 1908-05-26 Frank I Clark Inhaler.
US1087186A (en) 1909-03-22 1914-02-17 Socrates Scholfield Illustrative educational device.
US1034123A (en) 1911-09-15 1912-07-30 Annie C Knowlson Nostril-expander.
US1077574A (en) 1913-01-15 1913-11-04 Henry R Woodward Nostril-expander.
US1139357A (en) 1913-07-02 1915-05-11 Charles A Garske Inhaler.
US1160797A (en) 1915-03-06 1915-11-16 Knute F Wallin Nasal inhaler.
US1256188A (en) 1915-12-22 1918-02-12 George H Wilson Antisnoring device.
US1481581A (en) 1922-10-18 1924-01-22 Henry R Woodward Nostril expander
GB210982A (en) 1923-02-06 1924-02-14 John Turner Warburton Nasal dilator
US1839606A (en) * 1930-02-17 1932-01-05 George A Simmons Distender for nostrils
US2010485A (en) 1934-06-19 1935-08-06 Heath Webster Lafe Antisnoring device
US2151227A (en) 1937-02-12 1939-03-21 Pawelek Anthony Nasal insert
US2237954A (en) * 1939-06-30 1941-04-08 William R Wilson Nasal filter and inhaler
US2264153A (en) 1940-02-19 1941-11-25 Madeleine Pope Nasal appliance
US2335936A (en) * 1940-09-30 1943-12-07 Joseph T Hanlon Nasal dilating device
US2277390A (en) 1941-03-19 1942-03-24 Jose E Crespo Nasal inhaler
US2433565A (en) 1946-06-21 1947-12-30 Korman Alexander Nose filter
US2515756A (en) 1947-08-30 1950-07-18 Bove Charles Nasal appliance
US2569743A (en) 1949-04-11 1951-10-02 Carlock Marion Pomeroy Device to promote nasal breathing and prevent snoring
US2662297A (en) * 1949-12-05 1953-12-15 Georg E Reicherter Gauge for testing out-of-roundness and diameters of cylindrical holes
US2672138A (en) 1950-09-05 1954-03-16 Carlock Marion Pomeroy Device to promote nasal breathing and prevent snoring
US2663297A (en) 1953-01-19 1953-12-22 Harold G Belasco Nasal adapter for oxygen inhalation
US2784127A (en) 1954-06-02 1957-03-05 Eastman Kodak Co Plasticized monomeric adhesive compositions and articles prepared therefrom
US2890695A (en) * 1957-10-07 1959-06-16 Gustaf A Safstrom Nasal air filter
US3424152A (en) 1966-02-25 1969-01-28 Irene Dorsey Kuhlman Tone downer
US3463149A (en) 1968-07-05 1969-08-26 Theodor Albu Nose air filter
ES149951Y (es) 1969-06-30 1970-06-01 Ramos Caballero Dispositivo para facilitar la respiracion nasal.
US3747597A (en) 1971-11-03 1973-07-24 V Olivera Nasal filter
US3742943A (en) 1972-01-03 1973-07-03 O Malmin Rhinoplasty treatment, method, and apparatus
US3802426A (en) 1972-09-08 1974-04-09 M Sakamoto Nasal filter
US4120299A (en) 1976-04-23 1978-10-17 Russo Joseph J Snore-prevention article and process for manufacturing the same
US4105035A (en) 1976-11-17 1978-08-08 Agnus Rella Nasal prosthesis
US4221217A (en) * 1978-05-01 1980-09-09 Amezcua Saul O Nasal device
US4267831A (en) * 1979-09-24 1981-05-19 Aguilar Rogelio M Nasal air filter and medicament dispenser device
US4592357A (en) * 1981-05-21 1986-06-03 Ersek Robert A Septal splint
US4414977A (en) 1981-07-20 1983-11-15 Wisconsin Alumni Research Foundation Nasal dilator
US4573461A (en) 1981-07-29 1986-03-04 Lake Norman M Nasal sealer and filter
GB2126101B (en) 1982-08-20 1986-07-02 Reginald George Breeze Device for resisting breathing through the nose
USD279708S (en) 1982-10-28 1985-07-16 Child Laboratories Inc. Teat implant
US4444933A (en) 1982-12-02 1984-04-24 Borden, Inc. Adhesive cyanoacrylate compositions with reduced adhesion to skin
US6217911B1 (en) 1995-05-22 2001-04-17 The United States Of America As Represented By The Secretary Of The Army sustained release non-steroidal, anti-inflammatory and lidocaine PLGA microspheres
GB8627600D0 (en) 1986-11-19 1986-12-17 Petruson B Nasal device
CA1340994C (en) 1989-09-21 2000-05-16 Rudolf Edgar Dr. Falk Treatment of conditions and disease
US5533499A (en) * 1991-06-10 1996-07-09 Creative Integration & Design, Inc. Nasal dilator
US5792753A (en) 1991-07-03 1998-08-11 Hyal Pharmaceutical Corporation Compositions comprising hyaluronic acid and prostaglandin-synthesis-inhibiting drugs
DE69331387T2 (de) 1992-09-10 2002-08-22 Childrens Medical Center Biodegradierbare polymeren matrizen mit verzoegerter freisetzung von lokalanaesthetika
US5700485A (en) 1992-09-10 1997-12-23 Children's Medical Center Corporation Prolonged nerve blockade by the combination of local anesthetic and glucocorticoid
US5417205A (en) * 1994-06-07 1995-05-23 Wang; Jen-Yi Air filter for the nose
US5425359A (en) 1994-08-29 1995-06-20 Liou; Nan-Tien Nose plug structure with filter
HUP9700322A3 (en) 1995-06-09 2001-03-28 Euro Celtique Sa Formulations and methods for providing prolonged local anesthesia
US5601594A (en) * 1995-09-14 1997-02-11 Best; Barry D. Nasal stent
US6063405A (en) 1995-09-29 2000-05-16 L.A.M. Pharmaceuticals, Llc Sustained release delivery system
US5816241A (en) 1995-09-29 1998-10-06 Cook; Lori Irene Coiled nasal dilator
US5725547A (en) 1996-01-04 1998-03-10 Chuter; Timothy A. M. Corrugated stent
US6096728A (en) 1996-02-09 2000-08-01 Amgen Inc. Composition and method for treating inflammatory diseases
US5853422A (en) 1996-03-22 1998-12-29 Scimed Life Systems, Inc. Apparatus and method for closing a septal defect
US5603317A (en) * 1996-03-25 1997-02-18 Farmer; Charlene C. Environmental mask
US5665104A (en) 1996-08-20 1997-09-09 Lee; Chi Hao Edwin Breathing enhancer
US6046187A (en) 1996-09-16 2000-04-04 Children's Medical Center Corporation Formulations and methods for providing prolonged local anesthesia
US6106541A (en) * 1997-05-16 2000-08-22 Hurbis; Charles G. Surgically implantable nasal dilator
US5775335A (en) 1997-05-29 1998-07-07 Seal; Daniel J. Apparatus to diminish or eliminate snoring
US5931852A (en) * 1997-06-04 1999-08-03 Brennan; H. George Nose airway device
BR9815499A (pt) 1997-07-02 2001-01-02 Euro Celtique Sa Anestesia prolongada nas juntas e nos espacos corporais.
US5941244A (en) * 1997-07-29 1999-08-24 Mitsumasa Chino Dustproof mask
US6511958B1 (en) 1997-08-14 2003-01-28 Sulzer Biologics, Inc. Compositions for regeneration and repair of cartilage lesions
DE69714035T2 (de) 1997-08-14 2003-03-06 Sulzer Innotec Ag, Winterthur Zusammensetzung und Vorrichtung zur Reparatur von Knorpelgewebe in vivo bestehend aus Nanokapseln mit osteoinduktiven und/oder chondroinduktiven Faktoren
US5895409A (en) 1997-09-16 1999-04-20 Mehdizadeh; Hamid Nasal dilator
TW577758B (en) 1997-10-27 2004-03-01 Ssp Co Ltd Intra-articular preparation for the treatment of arthropathy
US6017315A (en) * 1998-02-25 2000-01-25 Respironics, Inc. Patient monitor and method of using same
US5925060A (en) 1998-03-13 1999-07-20 B. Braun Celsa Covered self-expanding vascular occlusion device
US6004342A (en) * 1998-03-26 1999-12-21 Filis; Elias A. Nasal insert device for improving breathing
US6451335B1 (en) 1998-07-02 2002-09-17 Euro-Celtique S.A. Formulations and methods for providing prolonged local anesthesia
US6537248B2 (en) * 1998-07-07 2003-03-25 Medtronic, Inc. Helical needle apparatus for creating a virtual electrode used for the ablation of tissue
US6346519B1 (en) 1998-09-09 2002-02-12 Advanced Medical Instruments Method and composition for treating arthritis
IT1302534B1 (it) 1998-12-21 2000-09-05 Fidia Advanced Biopolymers Srl Composizioni iniettabili, biocompatibili e biodegradabili comprendentialmeno un derivato dell'acido ialuronico, cellule condrogeniche, per
US6528107B2 (en) 1999-01-19 2003-03-04 Sulzer Carbomedics Inc. Method for producing antimicrobial antithrombogenic medical devices
DE19903782C1 (de) 1999-02-01 2000-07-13 Alexander Loschke Drahtkörper zur Anordnung in den Nasenöffnungen eines Menschen
US6893450B2 (en) 1999-03-26 2005-05-17 Cook Urological Incorporated Minimally-invasive medical retrieval device
SE9901257D0 (sv) 1999-04-09 1999-04-09 Hel Ab Behandling av smärta efter ledoperation
US6582715B1 (en) 1999-04-27 2003-06-24 Agion Technologies, Inc. Antimicrobial orthopedic implants
US6193704B1 (en) 1999-06-10 2001-02-27 Thomas F. Winters Site-specific postoperative pain relief system, fit and method
US6386197B1 (en) * 2000-01-27 2002-05-14 Brook D. Miller Nasal air passageway opening device
AUPQ582100A0 (en) 2000-02-24 2000-03-16 Irm Technologies Pty Ltd Nasal filter and sampler
US6602282B1 (en) 2000-05-04 2003-08-05 Avantec Vascular Corporation Flexible stent structure
US6561188B1 (en) 2000-08-21 2003-05-13 Ellis Alan D Nasal breathing apparatus and methods
US6527760B1 (en) 2000-09-25 2003-03-04 Vijay B. Vad Out-patient joint lavage kit and protocol
US6416540B1 (en) 2000-11-01 2002-07-09 Sandip V. Mathur Magnetically actuated cleanable stent and method
JP2004537495A (ja) 2000-11-03 2004-12-16 コントロール・デリバリー・システムズ 関節疾患を治療するための改善された装置及び方法
US6590059B2 (en) 2001-05-11 2003-07-08 Ap Pharma, Inc. Bioerodible polyorthoesters from dioxolane-based diketene acetals
US9242080B2 (en) 2001-05-22 2016-01-26 Sanostec Corp Nasal inserts
US8403954B2 (en) 2001-05-22 2013-03-26 Sanostec Corp. Nasal congestion, obstruction relief, and drug delivery
US6562057B2 (en) 2001-05-22 2003-05-13 Ernest Santin Nasal breathing assist devices
IL159624A0 (en) 2001-06-29 2004-06-01 Medgraft Microtech Inc Biodegradable injectable implants and related methods of manufacture and use
US6679265B2 (en) 2001-10-25 2004-01-20 Worldwide Medical Technologies Nasal cannula
US6524606B1 (en) 2001-11-16 2003-02-25 Ap Pharma, Inc. Bioerodible polyorthoesters containing amine groups
GB2382776A (en) 2001-11-21 2003-06-11 Tayside Flow Technologies Ltd Helix shaped insert for flow modification in a duct or stent
US6863066B2 (en) 2002-01-28 2005-03-08 Ronald Jack Ogle Adjustable nasal dilator filter
US6547634B1 (en) 2002-05-13 2003-04-15 Far Great Plastics Industrial Co., Ltd. Toy car
JP2002301152A (ja) 2002-05-22 2002-10-15 Bio International Kk 鼻マスク
AU2003276999A1 (en) 2002-09-26 2004-04-19 Savacor, Inc. Cardiovascular anchoring device and method of deploying same
US20040147954A1 (en) 2003-01-14 2004-07-29 Wood Charles E. Internal nasal dilator
WO2004069110A1 (en) 2003-02-10 2004-08-19 VANGSGAARD, Jørgen Nasal insertable device for facilitating breathing through the nose
US8480706B2 (en) 2003-07-14 2013-07-09 W.L. Gore & Associates, Inc. Tubular patent foramen ovale (PFO) closure device with catch system
CA2589922A1 (en) * 2004-12-08 2006-06-15 Ventus Medical, Inc. Respiratory devices and methods of use
US6978781B1 (en) 2005-03-11 2005-12-27 John Jordan Nasal dilator
WO2007001992A2 (en) 2005-06-21 2007-01-04 Regents Of The University Of Minnesota Ureteral stent with axial and radial variability
US7637939B2 (en) 2005-06-30 2009-12-29 Boston Scientific Scimed, Inc. Hybrid stent
DE102005037843A1 (de) 2005-08-04 2007-02-08 Peter Rexin Nasen-Spirale
SE528848C2 (sv) 2005-08-05 2007-02-27 Ortoma Ab Anordning för operativt ingrepp eller sårbildning
US8702777B2 (en) 2005-08-22 2014-04-22 Incept, Llc Steep-taper flared stents and apparatus and methods for delivering them
US7393269B2 (en) * 2005-09-16 2008-07-01 3M Innovative Properties Company Abrasive filter assembly and methods of making same
KR101074876B1 (ko) 2006-02-13 2011-10-19 레트로배스큘러, 아이엔씨. 제어된 전방성 및 역방성 트래킹을 이용한 폐색된 혈관의 재개통
US20070239199A1 (en) 2006-03-31 2007-10-11 Swaminathan Jayaraman Inferior vena cava filter
CA2653139C (en) 2006-05-23 2016-01-05 Ventus Medical, Inc. Nasal respiratory devices
BRPI0711784B8 (pt) 2006-06-15 2021-06-22 Microvention Inc dispositivo de embolização construído de polímero expansível e seu método de preparação
WO2008058367A1 (en) 2006-11-16 2008-05-22 Moore Corey C Nasal dilation device
US20130109987A1 (en) 2011-05-12 2013-05-02 Medical Device Innovations Inc. Method and device for treatment of arrhythmias and other maladies

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11192251A (ja) * 1997-12-29 1999-07-21 Hidetoshi Araki イビキの防止方法及び防止器
US20050021073A1 (en) * 2001-05-22 2005-01-27 Ernest Santin Nasal congestion and obstruction relief and breathing assist devices
WO2004026391A1 (en) * 2002-09-18 2004-04-01 Asap Breathe Assist Pty Ltd A nasal cavity dilator

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO2007065083A2 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USD774648S1 (en) 2013-07-18 2016-12-20 Asap Breatheassist Pty Ltd Nasal dilator device
USD759239S1 (en) 2013-12-06 2016-06-14 Asap Breatheassist Pty Ltd Nasal dilator device
USD753821S1 (en) 2014-06-20 2016-04-12 Asap Breatheassist Pty Ltd Nasal dilator device
USD754851S1 (en) 2014-06-20 2016-04-26 Asap Breatheassist Pty Ltd Nasal dilator device
USD754850S1 (en) 2014-06-20 2016-04-26 Asap Breatheassist Pty Ltd Nasal dilator device
US11259908B2 (en) 2016-07-20 2022-03-01 Elanco Us Inc. Animal intranasal administration device, systems, and associated methods
USD952141S1 (en) 2019-06-13 2022-05-17 Asap Breatheassist Pty Ltd Nasal dilator device
RU195387U1 (ru) * 2019-12-05 2020-01-24 Общество с ограниченной ответственностью Компания "Динамика" Ингалятор для носа

Also Published As

Publication number Publication date
US20060085027A1 (en) 2006-04-20
AU2006320231A1 (en) 2007-06-07
US20130296809A1 (en) 2013-11-07
US10639186B2 (en) 2020-05-05
EP1968684A4 (de) 2009-12-02
WO2007065083A2 (en) 2007-06-07
CA2635738C (en) 2015-09-29
US20210085508A1 (en) 2021-03-25
US8403954B2 (en) 2013-03-26
US9504599B2 (en) 2016-11-29
WO2007065083A3 (en) 2008-10-02
CA2894348A1 (en) 2007-06-07
EP1968684B1 (de) 2016-02-24
CN101616708A (zh) 2009-12-30
CN101616708B (zh) 2013-05-29
CA2894348C (en) 2017-04-25
US20170071777A1 (en) 2017-03-16
CA2635738A1 (en) 2007-06-07

Similar Documents

Publication Publication Date Title
US20210085508A1 (en) Nasal congestion, obstruction relief, and drug delivery
US20170273626A1 (en) Nasal insert having one or more sensors
US20110238016A1 (en) Drug delivery to a joint
US6740333B2 (en) Suppository and composition comprising at least one polyethylene glycol
US8491622B2 (en) Multi-layer internal nasal dilator with tubular expanders and compound delivery protrusions
AU619169B2 (en) Nasal devices
JP2005523077A (ja) 抗肉芽腫剤を形成する特性を備えた胃瘻造設術又は空腸造瘻術に使用される薄型の組合せ装置
US20070026527A1 (en) Means for detecting pathological transformation of the app protein and their uses
WO2012035427A1 (en) Nasal delivery
EP1802282A1 (de) Biokompatible proteinteilchen, teilchenvorrichtungen und verfahren dafür
WO2020214863A1 (en) Biodegradable nasal splint
AU2013209347B2 (en) Nasal congestion, obstruction relief, and drug delivery
JP2005517653A5 (de)
WO2008066459A1 (en) Plug to be introduced into a passage such as nasal passage
US8343464B2 (en) Composition and method for treating eustachian tube dysfunction
EP1301175B1 (de) Suppositorium und zusammensetzung enthaltend mindestens ein polyethylenglycol
JPWO2016204026A1 (ja) 鼻腔留置デバイス
Hansen Continuous acoustic rhinometry (RHIN2000) evaluating the influence of nasally administered glucagon in healthy volunteers during and after common cold

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20080627

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA HR MK RS

R17D Deferred search report published (corrected)

Effective date: 20081002

A4 Supplementary search report drawn up and despatched

Effective date: 20091104

RIC1 Information provided on ipc code assigned before grant

Ipc: A61M 29/00 20060101ALI20091029BHEP

Ipc: A61F 5/08 20060101AFI20091029BHEP

17Q First examination report despatched

Effective date: 20100121

DAX Request for extension of the european patent (deleted)
REG Reference to a national code

Ref country code: DE

Ref legal event code: R079

Ref document number: 602006048049

Country of ref document: DE

Free format text: PREVIOUS MAIN CLASS: A61M0029000000

Ipc: A61F0005080000

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

RIC1 Information provided on ipc code assigned before grant

Ipc: A61M 15/08 20060101ALI20150819BHEP

Ipc: A61M 29/00 20060101ALI20150819BHEP

Ipc: A61M 16/06 20060101ALI20150819BHEP

Ipc: A61F 5/08 20060101AFI20150819BHEP

Ipc: A61M 31/00 20060101ALI20150819BHEP

INTG Intention to grant announced

Effective date: 20150908

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 776266

Country of ref document: AT

Kind code of ref document: T

Effective date: 20160315

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602006048049

Country of ref document: DE

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG4D

REG Reference to a national code

Ref country code: NL

Ref legal event code: MP

Effective date: 20160224

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK05

Ref document number: 776266

Country of ref document: AT

Kind code of ref document: T

Effective date: 20160224

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160525

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160624

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 11

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602006048049

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed

Effective date: 20161125

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160524

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20161130

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20161130

REG Reference to a national code

Ref country code: IE

Ref legal event code: MM4A

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20161130

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 12

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20161128

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO

Effective date: 20061128

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160224

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20231019

Year of fee payment: 18

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20231024

Year of fee payment: 18

Ref country code: DE

Payment date: 20231017

Year of fee payment: 18